Inhibition of the Nrf2-TrxR Axis Sensitizes the Drug-Resistant Chronic Myelogenous Leukemia Cell Line K562/G01 to Imatinib Treatments
Identifieur interne : 000670 ( Pmc/Checkpoint ); précédent : 000669; suivant : 000671Inhibition of the Nrf2-TrxR Axis Sensitizes the Drug-Resistant Chronic Myelogenous Leukemia Cell Line K562/G01 to Imatinib Treatments
Auteurs : Lianrong Xu [République populaire de Chine] ; Yan Zhao [République populaire de Chine] ; Fei Pan [République populaire de Chine] ; Mengxia Zhu [République populaire de Chine] ; Liqin Yao [République populaire de Chine] ; Yan Liu [République populaire de Chine] ; Jiangfang Feng [République populaire de Chine] ; Jie Xiong [République populaire de Chine] ; Xiuhua Chen [République populaire de Chine] ; Fanggang Ren [République populaire de Chine] ; Yanhong Tan [République populaire de Chine] ; Hongwei Wang [République populaire de Chine]Source :
- BioMed Research International [ 2314-6133 ] ; 2019.
Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in tumor drug resistance, but its role in imatinib resistance of chronic myeloid leukemia (CML) remains elusive. We aimed to investigate the effects of Nrf2 on drug sensitivity, thioredoxin reductase (TrxR) expression, reactive oxygen species (ROS) production, and apoptosis induction in imatinib-resistant CML K562/G01 cells and explored their potential mechanisms. Stable K562/G01 cells with knockdown of Nrf2 were established by infection of siRNA-expressing lentivirus. The mRNA and protein expression levels of Nrf2 and TrxR were determined by real-time quantitative polymerase chain reaction and western blot, respectively. ROS generation and apoptosis were assayed by flow cytometry, while drug sensitivity was measured by the Cell Counting Kit-8 assay. Imatinib-resistant K562/G01 cells had higher levels of Nrf2 expression than the parental K562 cells at both mRNA and protein levels. Expression levels of Nrf2 and TrxR were positively correlated in K562/G01 cells. Knockdown of Nrf2 in K562/G01 cells enhanced the intracellular ROS level, suppressed cell proliferation, and increased apoptosis in response to imatinib treatments. Nrf2 expression contributes to the imatinib resistance of K562/G01 cells and is positively correlated with TrxR expression. Targeted inhibition of the Nrf2-TrxR axis represents a potential therapeutic approach for imatinib-resistant CML.
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DOI: 10.1155/2019/6502793
PubMed: 31828114
PubMed Central: 6885806
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China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Pan, Fei" sort="Pan, Fei" uniqKey="Pan F" first="Fei" last="Pan">Fei Pan</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Zhu, Mengxia" sort="Zhu, Mengxia" uniqKey="Zhu M" first="Mengxia" last="Zhu">Mengxia Zhu</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of 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id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Feng, Jiangfang" sort="Feng, Jiangfang" uniqKey="Feng J" first="Jiangfang" last="Feng">Jiangfang Feng</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Xiong, Jie" sort="Xiong, Jie" uniqKey="Xiong J" first="Jie" last="Xiong">Jie Xiong</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Xiuhua" sort="Chen, Xiuhua" uniqKey="Chen X" first="Xiuhua" last="Chen">Xiuhua Chen</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Ren, Fanggang" sort="Ren, Fanggang" uniqKey="Ren F" first="Fanggang" last="Ren">Fanggang Ren</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Tan, Yanhong" sort="Tan, Yanhong" uniqKey="Tan Y" first="Yanhong" last="Tan">Yanhong Tan</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Hongwei" sort="Wang, Hongwei" uniqKey="Wang H" first="Hongwei" last="Wang">Hongwei Wang</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31828114</idno><idno type="pmc">6885806</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885806</idno><idno type="RBID">PMC:6885806</idno><idno type="doi">10.1155/2019/6502793</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000423</idno><idno 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Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Zhao, Yan" sort="Zhao, Yan" uniqKey="Zhao Y" first="Yan" last="Zhao">Yan Zhao</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Pan, Fei" sort="Pan, Fei" uniqKey="Pan F" first="Fei" last="Pan">Fei Pan</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Zhu, Mengxia" sort="Zhu, Mengxia" uniqKey="Zhu M" first="Mengxia" last="Zhu">Mengxia Zhu</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Yao, Liqin" sort="Yao, Liqin" uniqKey="Yao L" first="Liqin" last="Yao">Liqin Yao</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Yan" sort="Liu, Yan" uniqKey="Liu Y" first="Yan" last="Liu">Yan Liu</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Feng, Jiangfang" sort="Feng, Jiangfang" uniqKey="Feng J" first="Jiangfang" last="Feng">Jiangfang Feng</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Xiong, Jie" sort="Xiong, Jie" uniqKey="Xiong J" first="Jie" last="Xiong">Jie Xiong</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Xiuhua" sort="Chen, Xiuhua" uniqKey="Chen X" first="Xiuhua" last="Chen">Xiuhua Chen</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Ren, Fanggang" sort="Ren, Fanggang" uniqKey="Ren F" first="Fanggang" last="Ren">Fanggang Ren</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Tan, Yanhong" sort="Tan, Yanhong" uniqKey="Tan Y" first="Yanhong" last="Tan">Yanhong Tan</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Hongwei" sort="Wang, Hongwei" uniqKey="Wang H" first="Hongwei" last="Wang">Hongwei Wang</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001</wicri:regionArea><wicri:noRegion>Shanxi 030001</wicri:noRegion></affiliation></author></analytic><series><title level="j">BioMed Research International</title><idno type="ISSN">2314-6133</idno><idno type="eISSN">2314-6141</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in tumor drug resistance, but its role in imatinib resistance of chronic myeloid leukemia (CML) remains elusive. We aimed to investigate the effects of Nrf2 on drug sensitivity, thioredoxin reductase (TrxR) expression, reactive oxygen species (ROS) production, and apoptosis induction in imatinib-resistant CML K562/G01 cells and explored their potential mechanisms. Stable K562/G01 cells with knockdown of Nrf2 were established by infection of siRNA-expressing lentivirus. The mRNA and protein expression levels of Nrf2 and TrxR were determined by real-time quantitative polymerase chain reaction and western blot, respectively. ROS generation and apoptosis were assayed by flow cytometry, while drug sensitivity was measured by the Cell Counting Kit-8 assay. Imatinib-resistant K562/G01 cells had higher levels of Nrf2 expression than the parental K562 cells at both mRNA and protein levels. Expression levels of Nrf2 and TrxR were positively correlated in K562/G01 cells. Knockdown of Nrf2 in K562/G01 cells enhanced the intracellular ROS level, suppressed cell proliferation, and increased apoptosis in response to imatinib treatments. Nrf2 expression contributes to the imatinib resistance of K562/G01 cells and is positively correlated with TrxR expression. Targeted inhibition of the Nrf2-TrxR axis represents a potential therapeutic approach for imatinib-resistant CML.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Flis, S" uniqKey="Flis S">S. Flis</name></author><author><name sortKey="Chojnacki, T" uniqKey="Chojnacki T">T. Chojnacki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stagno, F" uniqKey="Stagno F">F. Stagno</name></author><author><name sortKey="Stella, S" uniqKey="Stella S">S. Stella</name></author><author><name sortKey="Spitaleri, A" uniqKey="Spitaleri A">A. Spitaleri</name></author><author><name sortKey="Pennisi, M S" uniqKey="Pennisi M">M. S. Pennisi</name></author><author><name sortKey="Di Raimondo, F" uniqKey="Di Raimondo F">F. Di Raimondo</name></author><author><name sortKey="Vigneri, P" uniqKey="Vigneri P">P. Vigneri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Milojkovic, D" uniqKey="Milojkovic D">D. Milojkovic</name></author><author><name sortKey="Apperley, J" uniqKey="Apperley J">J. Apperley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, T" uniqKey="Kim T">T. Kim</name></author><author><name sortKey="Tyndel, M S" uniqKey="Tyndel M">M. S. Tyndel</name></author><author><name sortKey="Kim, H J" uniqKey="Kim H">H. J. Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Soverini, S" uniqKey="Soverini S">S. Soverini</name></author><author><name sortKey="Mancini, M" uniqKey="Mancini M">M. Mancini</name></author><author><name sortKey="Bavaro, L" uniqKey="Bavaro L">L. Bavaro</name></author><author><name sortKey="Cavo, M" uniqKey="Cavo M">M. Cavo</name></author><author><name sortKey="Martinelli, G" uniqKey="Martinelli G">G. Martinelli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Itoh, K" uniqKey="Itoh K">K. Itoh</name></author><author><name sortKey="Wakabayashi, N" uniqKey="Wakabayashi N">N. Wakabayashi</name></author><author><name sortKey="Katoh, Y" uniqKey="Katoh Y">Y. Katoh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neumann, C A" uniqKey="Neumann C">C. A. Neumann</name></author><author><name sortKey="Cao, J" uniqKey="Cao J">J. Cao</name></author><author><name sortKey="Manevich, Y" uniqKey="Manevich Y">Y. Manevich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abdul Aziz, A" uniqKey="Abdul Aziz A">A. Abdul-Aziz</name></author><author><name sortKey="Macewan, D J" uniqKey="Macewan D">D. J. MacEwan</name></author><author><name sortKey="Bowles, K M" uniqKey="Bowles K">K. M. Bowles</name></author><author><name sortKey="Rushworth, S A" uniqKey="Rushworth S">S. A. Rushworth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Radwan, S M" uniqKey="Radwan S">S. M. Radwan</name></author><author><name sortKey="Hamdy, N M" uniqKey="Hamdy N">N. M. Hamdy</name></author><author><name sortKey="Hegab, H M" uniqKey="Hegab H">H. M. Hegab</name></author><author><name sortKey="El Mesallamy, H O" uniqKey="El Mesallamy H">H. O. El-Mesallamy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhumina, A" uniqKey="Zhumina A">A. Zhumina</name></author><author><name sortKey="Pogossyan, G" uniqKey="Pogossyan G">G. Pogossyan</name></author><author><name sortKey="Li, K" uniqKey="Li K">K. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, P" uniqKey="Lin P">P. Lin</name></author><author><name sortKey="Ren, Y" uniqKey="Ren Y">Y. Ren</name></author><author><name sortKey="Yan, X" uniqKey="Yan X">X. Yan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Su, X" uniqKey="Su X">X. Su</name></author><author><name sortKey="Jiang, X" uniqKey="Jiang X">X. Jiang</name></author><author><name sortKey="Meng, L" uniqKey="Meng L">L. Meng</name></author><author><name sortKey="Dong, X" uniqKey="Dong X">X. Dong</name></author><author><name sortKey="Shen, Y" uniqKey="Shen Y">Y. Shen</name></author><author><name sortKey="Xin, Y" uniqKey="Xin Y">Y. Xin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bai, X" uniqKey="Bai X">X. Bai</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y. Chen</name></author><author><name sortKey="Hou, X" uniqKey="Hou X">X. Hou</name></author><author><name sortKey="Huang, M" uniqKey="Huang M">M. Huang</name></author><author><name sortKey="Jin, J" uniqKey="Jin J">J. Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rushworth, S A" uniqKey="Rushworth S">S. A. Rushworth</name></author><author><name sortKey="Macewan, D J" uniqKey="Macewan D">D. J. Macewan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rushworth, S A" uniqKey="Rushworth S">S. A. Rushworth</name></author><author><name sortKey="Zaitseva, L" uniqKey="Zaitseva L">L. Zaitseva</name></author><author><name sortKey="Murray, M Y" uniqKey="Murray M">M. Y. Murray</name></author><author><name sortKey="Shah, N M" uniqKey="Shah N">N. M. Shah</name></author><author><name sortKey="Bowles, K M" uniqKey="Bowles K">K. M. Bowles</name></author><author><name sortKey="Macewan, D J" uniqKey="Macewan D">D. J. MacEwan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karathedath, S" uniqKey="Karathedath S">S. Karathedath</name></author><author><name sortKey="Rajamani, B M" uniqKey="Rajamani B">B. M. Rajamani</name></author><author><name sortKey="Aalam, S M M" uniqKey="Aalam S">S. M. M. Aalam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, X" uniqKey="Xu X">X. Xu</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X. Zhang</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Han, X" uniqKey="Han X">X. Han</name></author><author><name sortKey="Liu, R" uniqKey="Liu R">R. Liu</name></author><author><name sortKey="Fang, J" uniqKey="Fang J">J. Fang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kamal, A M" uniqKey="Kamal A">A. M. Kamal</name></author><author><name sortKey="El Hefny, N H" uniqKey="El Hefny N">N. H. El-Hefny</name></author><author><name sortKey="Hegab, H M" uniqKey="Hegab H">H. M. Hegab</name></author><author><name sortKey="El Mesallamy, H O" uniqKey="El Mesallamy H">H. O. El-Mesallamy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, J J" uniqKey="Liu J">J. J. Liu</name></author><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q. Liu</name></author><author><name sortKey="Wei, H L" uniqKey="Wei H">H. L. Wei</name></author><author><name sortKey="Yi, J" uniqKey="Yi J">J. Yi</name></author><author><name sortKey="Zhao, H S" uniqKey="Zhao H">H. S. Zhao</name></author><author><name sortKey="Gao, L P" uniqKey="Gao L">L. P. Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pan, F" uniqKey="Pan F">F. Pan</name></author><author><name sortKey="Xu, L R" uniqKey="Xu L">L. R. Xu</name></author><author><name sortKey="Wang, H W" uniqKey="Wang H">H. W. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pan, F" uniqKey="Pan F">F. Pan</name></author><author><name sortKey="Xu, L R" uniqKey="Xu L">L. R. Xu</name></author><author><name sortKey="Wang, H W" uniqKey="Wang H">H. W. Wang</name></author><author><name sortKey="Zhu, M X" uniqKey="Zhu M">M. X. Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qi, J" uniqKey="Qi J">J. Qi</name></author><author><name sortKey="Peng, H" uniqKey="Peng H">H. Peng</name></author><author><name sortKey="Gu, Z L" uniqKey="Gu Z">Z. L. Gu</name></author><author><name sortKey="Liang, Z Q" uniqKey="Liang Z">Z. Q. Liang</name></author><author><name sortKey="Yang, C Z" uniqKey="Yang C">C. Z. Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Livak, K J" uniqKey="Livak K">K. J. Livak</name></author><author><name sortKey="Schmittgen, T D" uniqKey="Schmittgen T">T. D. Schmittgen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bonovolias, I D" uniqKey="Bonovolias I">I. D. Bonovolias</name></author><author><name sortKey="Tsiftsoglou, A S" uniqKey="Tsiftsoglou A">A. S. Tsiftsoglou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nagai, T" uniqKey="Nagai T">T. Nagai</name></author><author><name sortKey="Kikuchi, S" uniqKey="Kikuchi S">S. Kikuchi</name></author><author><name sortKey="Ohmine, K" uniqKey="Ohmine K">K. Ohmine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cebula, M" uniqKey="Cebula M">M. Cebula</name></author><author><name sortKey="Schmidt, E E" uniqKey="Schmidt E">E. E. Schmidt</name></author><author><name sortKey="Arner, E S J" uniqKey="Arner E">E. S. J. Arnér</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raninga, P V" uniqKey="Raninga P">P. V. Raninga</name></author><author><name sortKey="Di Trapani, G" uniqKey="Di Trapani G">G. Di Trapani</name></author><author><name sortKey="Vuckovic, S" uniqKey="Vuckovic S">S. Vuckovic</name></author><author><name sortKey="Tonissen, K F" uniqKey="Tonissen K">K. F. Tonissen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Xu, L R" uniqKey="Xu L">L. R. Xu</name></author><author><name sortKey="Zhu, M X" uniqKey="Zhu M">M. X. Zhu</name></author><author><name sortKey="Pan, F" uniqKey="Pan F">F. Pan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Renschler, M F" uniqKey="Renschler M">M. F. Renschler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Toler, S M" uniqKey="Toler S">S. M. Toler</name></author><author><name sortKey="Noe, D" uniqKey="Noe D">D. Noe</name></author><author><name sortKey="Sharma, A" uniqKey="Sharma A">A. Sharma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sattler, M" uniqKey="Sattler M">M. Sattler</name></author><author><name sortKey="Verma, S" uniqKey="Verma S">S. Verma</name></author><author><name sortKey="Shrikhande, G" uniqKey="Shrikhande G">G. Shrikhande</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, J H" uniqKey="Kim J">J. H. Kim</name></author><author><name sortKey="Chu, S C" uniqKey="Chu S">S. C. Chu</name></author><author><name sortKey="Gramlich, J L" uniqKey="Gramlich J">J. L. Gramlich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="No, J H" uniqKey="No J">J. H. No</name></author><author><name sortKey="Kim, Y B" uniqKey="Kim Y">Y. B. Kim</name></author><author><name sortKey="Song, Y S" uniqKey="Song Y">Y. S. Song</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raninga, P V" uniqKey="Raninga P">P. V. Raninga</name></author><author><name sortKey="Di Trapani, G" uniqKey="Di Trapani G">G. Di Trapani</name></author><author><name sortKey="Vuckovic, S" uniqKey="Vuckovic S">S. Vuckovic</name></author><author><name sortKey="Bhatia, M" uniqKey="Bhatia M">M. Bhatia</name></author><author><name sortKey="Tonissen, K F" uniqKey="Tonissen K">K. F. Tonissen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cho, J M" uniqKey="Cho J">J. M. Cho</name></author><author><name sortKey="Manandhar, S" uniqKey="Manandhar S">S. Manandhar</name></author><author><name sortKey="Lee, H R" uniqKey="Lee H">H. R. Lee</name></author><author><name sortKey="Park, H M" uniqKey="Park H">H. M. Park</name></author><author><name sortKey="Kwak, M K" uniqKey="Kwak M">M. K. Kwak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, K" uniqKey="Zhang K">K. Zhang</name></author><author><name sortKey="Yang, H" uniqKey="Yang H">H. Yang</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Ma, L" uniqKey="Ma L">L. Ma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shibata, T" uniqKey="Shibata T">T. Shibata</name></author><author><name sortKey="Kokubu, A" uniqKey="Kokubu A">A. Kokubu</name></author><author><name sortKey="Gotoh, M" uniqKey="Gotoh M">M. Gotoh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akhdar, H" uniqKey="Akhdar H">H. Akhdar</name></author><author><name sortKey="Loyer, P" uniqKey="Loyer P">P. Loyer</name></author><author><name sortKey="Rauch, C" uniqKey="Rauch C">C. Rauch</name></author><author><name sortKey="Corlu, A" uniqKey="Corlu A">A. Corlu</name></author><author><name sortKey="Guillouzo, A" uniqKey="Guillouzo A">A. Guillouzo</name></author><author><name sortKey="Morel, F" uniqKey="Morel F">F. Morel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, X J" uniqKey="Wang X">X. J. Wang</name></author><author><name sortKey="Sun, Z" uniqKey="Sun Z">Z. Sun</name></author><author><name sortKey="Villeneuve, N F" uniqKey="Villeneuve N">N. F. Villeneuve</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Biomed Res Int</journal-id><journal-id journal-id-type="iso-abbrev">Biomed Res Int</journal-id><journal-id journal-id-type="publisher-id">BMRI</journal-id><journal-title-group><journal-title>BioMed Research International</journal-title></journal-title-group><issn pub-type="ppub">2314-6133</issn><issn pub-type="epub">2314-6141</issn><publisher><publisher-name>Hindawi</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31828114</article-id><article-id pub-id-type="pmc">6885806</article-id><article-id pub-id-type="doi">10.1155/2019/6502793</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Inhibition of the Nrf2-TrxR Axis Sensitizes the Drug-Resistant Chronic Myelogenous Leukemia Cell Line K562/G01 to Imatinib Treatments</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0002-5279-6421</contrib-id><name><surname>Xu</surname><given-names>Lianrong</given-names></name><email>xulrdoctor@sxmu.edu.cn</email><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Yan</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Pan</surname><given-names>Fei</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Zhu</surname><given-names>Mengxia</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Yao</surname><given-names>Liqin</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Yan</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Feng</surname><given-names>Jiangfang</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Xiong</surname><given-names>Jie</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Xiuhua</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Ren</surname><given-names>Fanggang</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Tan</surname><given-names>Yanhong</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0002-2902-591X</contrib-id><name><surname>Wang</surname><given-names>Hongwei</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib></contrib-group><aff id="I1">Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China</aff><author-notes><fn fn-type="other"><p>Academic Editor: Nadia M. Hamdy</p></fn></author-notes><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>18</day><month>11</month><year>2019</year></pub-date><volume>2019</volume><elocation-id>6502793</elocation-id><history><date date-type="received"><day>25</day><month>6</month><year>2019</year></date><date date-type="accepted"><day>30</day><month>8</month><year>2019</year></date></history><permissions><copyright-statement>Copyright © 2019 Lianrong Xu et al.</copyright-statement><copyright-year>2019</copyright-year><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in tumor drug resistance, but its role in imatinib resistance of chronic myeloid leukemia (CML) remains elusive. We aimed to investigate the effects of Nrf2 on drug sensitivity, thioredoxin reductase (TrxR) expression, reactive oxygen species (ROS) production, and apoptosis induction in imatinib-resistant CML K562/G01 cells and explored their potential mechanisms. Stable K562/G01 cells with knockdown of Nrf2 were established by infection of siRNA-expressing lentivirus. The mRNA and protein expression levels of Nrf2 and TrxR were determined by real-time quantitative polymerase chain reaction and western blot, respectively. ROS generation and apoptosis were assayed by flow cytometry, while drug sensitivity was measured by the Cell Counting Kit-8 assay. Imatinib-resistant K562/G01 cells had higher levels of Nrf2 expression than the parental K562 cells at both mRNA and protein levels. Expression levels of Nrf2 and TrxR were positively correlated in K562/G01 cells. Knockdown of Nrf2 in K562/G01 cells enhanced the intracellular ROS level, suppressed cell proliferation, and increased apoptosis in response to imatinib treatments. Nrf2 expression contributes to the imatinib resistance of K562/G01 cells and is positively correlated with TrxR expression. Targeted inhibition of the Nrf2-TrxR axis represents a potential therapeutic approach for imatinib-resistant CML.</p></abstract><funding-group><award-group><funding-source>Natural Science Foundation of Shanxi Province</funding-source><award-id>2012011038-5</award-id></award-group><award-group><funding-source>Shanxi Medical and Health Science and Technology Plan Project</funding-source><award-id>20100202</award-id></award-group></funding-group></article-meta></front><floats-group><fig id="fig1" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Imatinib-resistant K562/G01 cells had higher levels of Nrf2 expression than the parental K562 cells. (a) The expression levels of Nrf2 mRNA in K562/G01 cells and K562 cells were quantitated by RT-qPCR. (b, c) The expression levels of Nrf2 protein in K562/G01 cells and K562 cells were evaluated by western blot assays. The representative images showed the bands of Nrf2 protein, and <italic>β</italic>-actin was taken as an internal control (b). The relative expression level of Nrf2 protein was quantitated by calculating the densitometry of targeted bands (c). <italic>n</italic> = 3 for each group; <sup><italic>∗</italic></sup><italic>p</italic> < 0.05, compared between the indicated two cell lines.</p></caption><graphic xlink:href="BMRI2019-6502793.001"></graphic></fig><fig id="fig2" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Verification of virus infection efficiency by monitoring GFP expression in K562/G01 cells. (a) Representative images of K562/G01 cells infected with Nrf2-RNAi-LV virus at 488 nm of the nominal optical excitation. Left: merged fluorescent images; middle: FITC fluorescent images; right: transmission photomicrograph at the bright light. Magnification, 10x. (b) Representative histogram plots showed the percentages of GFP-positive cells in uninfected blank K562/G01 cells, NC-GFP-LV-infected cells, and Nrf2-RNAi-LV-infected cells.</p></caption><graphic xlink:href="BMRI2019-6502793.002"></graphic></fig><fig id="fig3" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Identification of a positive correlation between Nrf2 expression and TrxR expression in K562/G01 cells. (a, b) The expression levels of Nrf2 mRNA (a) and TrxR mRNA (b) were quantitated in the indicated cells by RT-qPCR. K562/G01, uninfected blank K562/G01 cells; NC-GFP-LV, NC-GFP-LV lentivirus-infected stable K562/G01 cells; Nrf2-RNAi-LV, Nrf2-RNAi-LV lentivirus-infected stable K562/G01 cells. (c–e) The expression levels of Nrf2 protein and TrxR protein were quantitated in the indicated cells by western blot. The representative images showed the bands of targeted proteins, and <italic>β</italic>-actin was taken as an internal control (c). The relative expression levels of Nrf2 protein (d) and TrxR protein (e) were quantitated by calculating the densitometry of targeted bands. <italic>n</italic> = 3 for each group; <sup><italic>∗</italic></sup><italic>p</italic> < 0.05, compared with the blank K562/G01 cells group.</p></caption><graphic xlink:href="BMRI2019-6502793.003"></graphic></fig><fig id="fig4" orientation="portrait" position="float"><label>Figure 4</label><caption><p>Knockdown of Nrf2 in K562/G01 cells increased the ROS level.</p></caption><graphic xlink:href="BMRI2019-6502793.004"></graphic></fig><fig id="fig5" orientation="portrait" position="float"><label>Figure 5</label><caption><p>Knockdown of Nrf2-sensitized K562/G01 cells to imatinib treatments.</p></caption><graphic xlink:href="BMRI2019-6502793.005"></graphic></fig><fig id="fig6" orientation="portrait" position="float"><label>Figure 6</label><caption><p>Knockdown of Nrf2 significantly increased the apoptosis ratio of K562/G01 cells after imatinib treatments. (a) Representative flow cytometric profiles showed the Annexin V and PI staining patterns in indicated cell lines at 28 hours after treatments with 6 <italic>μ</italic>M and 20 <italic>μ</italic>M imatinib. (b) Summary data on the percentage of apoptosis ratio (Annexin V-positive cells among total cells) in the indicated cell lines treated with (6 <italic>μ</italic>M and 20 <italic>μ</italic>M) or without (0 <italic>μ</italic>M) imatinib. <italic>n</italic> = 3 for each group; <sup><italic>∗</italic></sup><italic>p</italic> < 0.05, compared with the control group and the blank K562/G01 cells group.</p></caption><graphic xlink:href="BMRI2019-6502793.006"></graphic></fig><table-wrap id="tab1" orientation="portrait" position="float"><label>Table 1</label><caption><p>Four siRNA sequences.</p></caption><table frame="hsides" rules="groups"><tbody><tr><td align="left" rowspan="1" colspan="1">No. 1 forward strand</td><td align="center" rowspan="1" colspan="1">GCAGCAAACAAGAGATGGCAA</td></tr><tr><td align="left" rowspan="1" colspan="1">No. 1 reverse strand</td><td align="center" rowspan="1" colspan="1">TTGCCATCTCTTGTTTGCTGC</td></tr><tr><td align="left" rowspan="1" colspan="1">No. 2 forward strand</td><td align="center" rowspan="1" colspan="1">GCACCTTATATCTCGAAGTTT</td></tr><tr><td align="left" rowspan="1" colspan="1">No. 2 reverse strand</td><td align="center" rowspan="1" colspan="1">AAACTTCGAGATATAAGGTGC</td></tr><tr><td align="left" rowspan="1" colspan="1">No. 3 forward strand</td><td align="center" rowspan="1" colspan="1">CCGGCATTTCACTAAACACAA</td></tr><tr><td align="left" rowspan="1" colspan="1">No. 3 reverse strand</td><td align="center" rowspan="1" colspan="1">TTGTGTTTAGTGAAATGCCGG</td></tr><tr><td align="left" rowspan="1" colspan="1">No. 4 forward strand</td><td align="center" rowspan="1" colspan="1">CCCTGTTGATTTAGACGGTAT</td></tr><tr><td align="left" rowspan="1" colspan="1">No. 4 reverse strand</td><td align="center" rowspan="1" colspan="1">ATACCGTCTAAATCAACAGGG</td></tr></tbody></table><table-wrap-foot><fn><p><italic>Note</italic>. No. 3 is the target sequence (from 5′ to 3′).</p></fn></table-wrap-foot></table-wrap><table-wrap id="tab2" orientation="portrait" position="float"><label>Table 2</label><caption><p>Target and control sequences established.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1"> </th><th align="center" rowspan="1" colspan="1">Sequence</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Frame structure</td><td align="center" rowspan="1" colspan="1">U6-vshRNA-CMV-GFP</td></tr><tr><td align="left" colspan="2" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="2" colspan="1">A framework to be established</td><td align="center" rowspan="1" colspan="1">5′-CCGG + sense strand + loop CTCGAG + antisense strand + TTTTTG-3′</td></tr><tr><td align="center" rowspan="1" colspan="1">5′-AATTCAAAAA + sense strand + loop CTCGAG + antisense strand-3′</td></tr><tr><td align="left" colspan="2" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="2" colspan="1">Targeted sequence (Nrf2-RNAi-LV)</td><td align="center" rowspan="1" colspan="1">Sense strand siRNA: CCGGCATTTCACTAAACACAA</td></tr><tr><td align="center" rowspan="1" colspan="1">Antisense strand siRNA: TTGTGTTTAGTGAAATGCCGG</td></tr><tr><td align="left" colspan="2" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Control sequence (NC-GFP-LV)</td><td align="center" rowspan="1" colspan="1">Target sequence: TTCTCCGAACGTGTCACGT</td></tr></tbody></table></table-wrap><table-wrap id="tab3" orientation="portrait" position="float"><label>Table 3</label><caption><p>Primer sequences of each gene used for RT-qPCR (from 5′ to 3′).</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Gene</th><th align="center" rowspan="1" colspan="1">GenBank serial number</th><th align="left" rowspan="1" colspan="1"> </th><th align="center" rowspan="1" colspan="1">Primer sequences</th><th align="center" rowspan="1" colspan="1">Product (bp)</th></tr></thead><tbody><tr><td align="left" rowspan="2" colspan="1">Nrf2</td><td rowspan="2" align="center" colspan="1">NM_006164.3</td><td align="center" rowspan="1" colspan="1">Forward</td><td align="center" rowspan="1" colspan="1">ACAATGAGGTTTCTTCGGCTAC</td><td rowspan="2" align="center" colspan="1">141</td></tr><tr><td align="center" rowspan="1" colspan="1">Reverse</td><td align="center" rowspan="1" colspan="1">CGTCTAAATCAACAGGGGCTAC</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="2" colspan="1">TrxR</td><td rowspan="2" align="center" colspan="1">NM_003330.2</td><td align="center" rowspan="1" colspan="1">Forward</td><td align="center" rowspan="1" colspan="1">TATCAGGAGGGCAGACTTCAA</td><td rowspan="2" align="center" colspan="1">153</td></tr><tr><td align="center" rowspan="1" colspan="1">Reverse</td><td align="center" rowspan="1" colspan="1">GACCATCACCTTCTTGCCATA</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="2" colspan="1">GAPDH</td><td rowspan="2" align="center" colspan="1">BC004109</td><td align="center" rowspan="1" colspan="1">Forward</td><td align="center" rowspan="1" colspan="1">AGAAGGCTGGGGCTCATTTG</td><td rowspan="2" align="center" colspan="1">258</td></tr><tr><td align="left" rowspan="1" colspan="1">Reverse</td><td align="center" rowspan="1" colspan="1">AGGGGCCATCCACAGTCTTC</td></tr></tbody></table></table-wrap><table-wrap id="tab4" orientation="portrait" position="float"><label>Table 4</label><caption><p>The impacts of siRNA-mediated Nrf2 knockdown to the mRNA expressions of Nrf2 and TrxR in K562/G01 cells.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Gene</th><th align="center" rowspan="1" colspan="1">Group</th><th align="center" rowspan="1" colspan="1">ΔCT (<inline-formula><mml:math id="M1"><mml:mrow><mml:mrow><mml:mover accent="true"><mml:mi>x</mml:mi><mml:mo>¯</mml:mo></mml:mover></mml:mrow><mml:mo>±</mml:mo><mml:mi>s</mml:mi></mml:mrow></mml:math></inline-formula>)</th><th align="center" rowspan="1" colspan="1">RQ (<inline-formula><mml:math id="M2"><mml:mrow><mml:mrow><mml:mover accent="true"><mml:mi>x</mml:mi><mml:mo>¯</mml:mo></mml:mover></mml:mrow><mml:mo>±</mml:mo><mml:mi>s</mml:mi></mml:mrow></mml:math></inline-formula>)</th></tr></thead><tbody><tr><td align="left" rowspan="3" colspan="1">Nrf2</td><td align="center" rowspan="1" colspan="1">K562/G01</td><td align="center" rowspan="1" colspan="1">3.15 ± 0.30</td><td align="center" rowspan="1" colspan="1">0.98 ± 0.21</td></tr><tr><td align="center" rowspan="1" colspan="1">NC-GFP-LV</td><td align="center" rowspan="1" colspan="1">3.23 ± 0.90</td><td align="center" rowspan="1" colspan="1">0.98 ± 0.44</td></tr><tr><td align="center" rowspan="1" colspan="1">Nrf2-RNAi-LV</td><td align="center" rowspan="1" colspan="1">4.63 ± 0.29</td><td align="center" rowspan="1" colspan="1">0.33 ± 0.09<sup><italic>∗</italic></sup></td></tr><tr><td align="left" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="3" colspan="1">TrxR</td><td align="center" rowspan="1" colspan="1">K562/G01</td><td align="center" rowspan="1" colspan="1">19.22 ± 0.25</td><td align="center" rowspan="1" colspan="1">1.01 ± 0.17</td></tr><tr><td align="center" rowspan="1" colspan="1">NC-GFP-LV</td><td align="center" rowspan="1" colspan="1">18.97 ± 0.68</td><td align="center" rowspan="1" colspan="1">0.92 ± 0.44</td></tr><tr><td align="center" rowspan="1" colspan="1">Nrf2-RNAi-LV</td><td align="center" rowspan="1" colspan="1">20.50 ± 0.31</td><td align="center" rowspan="1" colspan="1">0.42 ± 0.13<sup><italic>∗</italic></sup></td></tr></tbody></table><table-wrap-foot><fn><p><sup><italic>∗</italic></sup><italic>p</italic> < 0.05, compared with the uninfected K562/G01 group or NC-GFP-LV-infected group; <italic>n</italic> = 3 for each group.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Xu, Lianrong" sort="Xu, Lianrong" uniqKey="Xu L" first="Lianrong" last="Xu">Lianrong Xu</name></noRegion><name sortKey="Chen, Xiuhua" sort="Chen, Xiuhua" uniqKey="Chen X" first="Xiuhua" last="Chen">Xiuhua Chen</name><name sortKey="Feng, Jiangfang" sort="Feng, Jiangfang" uniqKey="Feng J" first="Jiangfang" last="Feng">Jiangfang Feng</name><name sortKey="Liu, Yan" sort="Liu, Yan" uniqKey="Liu Y" first="Yan" last="Liu">Yan Liu</name><name sortKey="Pan, Fei" sort="Pan, Fei" uniqKey="Pan F" first="Fei" last="Pan">Fei Pan</name><name sortKey="Ren, Fanggang" sort="Ren, Fanggang" uniqKey="Ren F" first="Fanggang" last="Ren">Fanggang Ren</name><name sortKey="Tan, Yanhong" sort="Tan, Yanhong" uniqKey="Tan Y" first="Yanhong" last="Tan">Yanhong Tan</name><name sortKey="Wang, Hongwei" sort="Wang, Hongwei" uniqKey="Wang H" first="Hongwei" last="Wang">Hongwei Wang</name><name sortKey="Xiong, Jie" sort="Xiong, Jie" uniqKey="Xiong J" first="Jie" last="Xiong">Jie Xiong</name><name sortKey="Yao, Liqin" sort="Yao, Liqin" uniqKey="Yao L" first="Liqin" last="Yao">Liqin Yao</name><name sortKey="Zhao, Yan" sort="Zhao, Yan" uniqKey="Zhao Y" first="Yan" last="Zhao">Yan Zhao</name><name sortKey="Zhu, Mengxia" sort="Zhu, Mengxia" uniqKey="Zhu M" first="Mengxia" last="Zhu">Mengxia Zhu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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