Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy
Identifieur interne : 000A65 ( Main/Exploration ); précédent : 000A64; suivant : 000A66Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy
Auteurs : Zheng Li [République populaire de Chine] ; Yongqiang Wang [République populaire de Chine] ; Linbo Wu [République populaire de Chine] ; Yalu Dong [République populaire de Chine] ; Jing Zhang [République populaire de Chine] ; Fan Chen [République populaire de Chine] ; Wei Xie [République populaire de Chine] ; Jianguo Huang [République populaire de Chine] ; Ning Lu [République populaire de Chine]Source :
- Oncology Reports [ 1021-335X ] ; 2019.
Abstract
Platinum-containing doublet chemotherapy is the cornerstone of lung cancer treatment; however, cisplatin resistance is a major obstacle in the treatment of lung cancer. However, the mechanism underlying this resistance has not been fully elucidated. Previous studies have shown that serum apurinic/apyrimidinic endonuclease 1 (APE1) levels in patients with NSCLC are inversely associated with progression-free survival after platinum-containing doublet chemotherapy, and can serve as a biomarker for predicting disease prognosis and treatment efficacy. The present study was designed to investigate the role played by APE1 in the resistance of lung cancer to cisplatin. The levels of mitochondrial apurinic endonuclease 1 (m-APE1) and total APE1 (t-APE1) protein in a cisplatin-resistant A549 cell line (A549/DDP) and cisplatin-sensitive A549 cells were analyzed by western blotting. Mitochondrial membrane potential was detected by using the JC-1 staining method. The cisplatin-resistance of APE1-overexpressing A549 cells and APE1-silenced A549/DDP cells was assessed by cell apoptosis and colony formation assays. The results revealed that cisplatin-resistant A549 cells contained high levels of APE1, and exhibited elevated levels of autophagy. The levels of m-APE1 and t-APE1 protein were increased in the A549/DDP cells when compared with these levels in the A549 cells. Overexpression of APE1 and Mia40 enhanced the cisplatin resistance and autophagy of the A549 cells. APE1 knockdown restored the cisplatin sensitivity and reduced the levels of LC3II and Parkin in the A549/DDP cells, but promoted the release of cytochrome
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DOI: 10.3892/or.2019.7345
PubMed: 31578585
PubMed Central: 6826301
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China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000</wicri:regionArea><wicri:noRegion>Xinjiang Uygur Autonomous Region 830000</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31578585</idno><idno type="pmc">6826301</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826301</idno><idno type="RBID">PMC:6826301</idno><idno type="doi">10.3892/or.2019.7345</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000753</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000753</idno><idno type="wicri:Area/Pmc/Curation">000753</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000753</idno><idno type="wicri:Area/Pmc/Checkpoint">000995</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000995</idno><idno type="wicri:Area/Ncbi/Merge">000A76</idno><idno type="wicri:Area/Ncbi/Curation">000A76</idno><idno type="wicri:Area/Ncbi/Checkpoint">000A76</idno><idno type="wicri:doubleKey">1021-335X:2019:Li Z:apurinic:endonuclease:promotes</idno><idno type="wicri:Area/Main/Merge">000A65</idno><idno type="wicri:Area/Main/Curation">000A65</idno><idno type="wicri:Area/Main/Exploration">000A65</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy</title><author><name sortKey="Li, Zheng" sort="Li, Zheng" uniqKey="Li Z" first="Zheng" last="Li">Zheng Li</name><affiliation wicri:level="1"><nlm:aff id="af1-or-0-0-7345">Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000</wicri:regionArea><wicri:noRegion>Xinjiang Uygur Autonomous Region 830000</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Yongqiang" sort="Wang, Yongqiang" uniqKey="Wang Y" first="Yongqiang" last="Wang">Yongqiang Wang</name><affiliation wicri:level="1"><nlm:aff id="af1-or-0-0-7345">Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000</wicri:regionArea><wicri:noRegion>Xinjiang Uygur Autonomous Region 830000</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Linbo" sort="Wu, Linbo" uniqKey="Wu L" first="Linbo" last="Wu">Linbo Wu</name><affiliation wicri:level="1"><nlm:aff id="af1-or-0-0-7345">Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000</wicri:regionArea><wicri:noRegion>Xinjiang Uygur Autonomous Region 830000</wicri:noRegion></affiliation></author><author><name sortKey="Dong, Yalu" sort="Dong, Yalu" uniqKey="Dong Y" first="Yalu" last="Dong">Yalu Dong</name><affiliation wicri:level="1"><nlm:aff id="af1-or-0-0-7345">Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000</wicri:regionArea><wicri:noRegion>Xinjiang Uygur Autonomous Region 830000</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Jing" sort="Zhang, Jing" uniqKey="Zhang J" first="Jing" last="Zhang">Jing Zhang</name><affiliation wicri:level="1"><nlm:aff id="af1-or-0-0-7345">Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000</wicri:regionArea><wicri:noRegion>Xinjiang Uygur Autonomous Region 830000</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Fan" sort="Chen, Fan" uniqKey="Chen F" first="Fan" last="Chen">Fan Chen</name><affiliation wicri:level="1"><nlm:aff id="af1-or-0-0-7345">Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000</wicri:regionArea><wicri:noRegion>Xinjiang Uygur Autonomous Region 830000</wicri:noRegion></affiliation></author><author><name sortKey="Xie, Wei" sort="Xie, Wei" uniqKey="Xie W" first="Wei" last="Xie">Wei Xie</name><affiliation wicri:level="1"><nlm:aff id="af1-or-0-0-7345">Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000</wicri:regionArea><wicri:noRegion>Xinjiang Uygur Autonomous Region 830000</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Jianguo" sort="Huang, Jianguo" uniqKey="Huang J" first="Jianguo" last="Huang">Jianguo Huang</name><affiliation wicri:level="1"><nlm:aff id="af1-or-0-0-7345">Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000</wicri:regionArea><wicri:noRegion>Xinjiang Uygur Autonomous Region 830000</wicri:noRegion></affiliation></author><author><name sortKey="Lu, Ning" sort="Lu, Ning" uniqKey="Lu N" first="Ning" last="Lu">Ning Lu</name><affiliation wicri:level="1"><nlm:aff id="af1-or-0-0-7345">Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Xinjiang Military Area General Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830000</wicri:regionArea><wicri:noRegion>Xinjiang Uygur Autonomous Region 830000</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncology Reports</title><idno type="ISSN">1021-335X</idno><idno type="eISSN">1791-2431</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>Platinum-containing doublet chemotherapy is the cornerstone of lung cancer treatment; however, cisplatin resistance is a major obstacle in the treatment of lung cancer. However, the mechanism underlying this resistance has not been fully elucidated. Previous studies have shown that serum apurinic/apyrimidinic endonuclease 1 (APE1) levels in patients with NSCLC are inversely associated with progression-free survival after platinum-containing doublet chemotherapy, and can serve as a biomarker for predicting disease prognosis and treatment efficacy. The present study was designed to investigate the role played by APE1 in the resistance of lung cancer to cisplatin. The levels of mitochondrial apurinic endonuclease 1 (m-APE1) and total APE1 (t-APE1) protein in a cisplatin-resistant A549 cell line (A549/DDP) and cisplatin-sensitive A549 cells were analyzed by western blotting. Mitochondrial membrane potential was detected by using the JC-1 staining method. The cisplatin-resistance of APE1-overexpressing A549 cells and APE1-silenced A549/DDP cells was assessed by cell apoptosis and colony formation assays. The results revealed that cisplatin-resistant A549 cells contained high levels of APE1, and exhibited elevated levels of autophagy. The levels of m-APE1 and t-APE1 protein were increased in the A549/DDP cells when compared with these levels in the A549 cells. Overexpression of APE1 and Mia40 enhanced the cisplatin resistance and autophagy of the A549 cells. APE1 knockdown restored the cisplatin sensitivity and reduced the levels of LC3II and Parkin in the A549/DDP cells, but promoted the release of cytochrome <italic>c</italic>. Furthermore, Parkin silencing or treatment with 3-methyladenine (3-MA, an autophagy inhibitor) promoted the apoptosis of APE1-overexpressing A549 cells, indicating that Parkin-mediated mitophagy plays an important role in the APE1-induced cisplatin resistance of A549 cells. In conclusion, APE1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Jemal, A" uniqKey="Jemal A">A Jemal</name></author><author><name sortKey="Bray, F" uniqKey="Bray F">F Bray</name></author><author><name sortKey="Center, Mm" uniqKey="Center M">MM Center</name></author><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J Ferlay</name></author><author><name sortKey="Ward, E" uniqKey="Ward E">E Ward</name></author><author><name sortKey="Forman, D" uniqKey="Forman D">D Forman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ren, J" uniqKey="Ren J">J Ren</name></author><author><name sortKey="Nie, Y" uniqKey="Nie Y">Y Nie</name></author><author><name sortKey="Lv, M" uniqKey="Lv M">M Lv</name></author><author><name sortKey="Shen, S" uniqKey="Shen S">S Shen</name></author><author><name sortKey="Tang, R" 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sortKey="Li, Zheng" sort="Li, Zheng" uniqKey="Li Z" first="Zheng" last="Li">Zheng Li</name></noRegion><name sortKey="Chen, Fan" sort="Chen, Fan" uniqKey="Chen F" first="Fan" last="Chen">Fan Chen</name><name sortKey="Dong, Yalu" sort="Dong, Yalu" uniqKey="Dong Y" first="Yalu" last="Dong">Yalu Dong</name><name sortKey="Huang, Jianguo" sort="Huang, Jianguo" uniqKey="Huang J" first="Jianguo" last="Huang">Jianguo Huang</name><name sortKey="Lu, Ning" sort="Lu, Ning" uniqKey="Lu N" first="Ning" last="Lu">Ning Lu</name><name sortKey="Wang, Yongqiang" sort="Wang, Yongqiang" uniqKey="Wang Y" first="Yongqiang" last="Wang">Yongqiang Wang</name><name sortKey="Wu, Linbo" sort="Wu, Linbo" uniqKey="Wu L" first="Linbo" last="Wu">Linbo Wu</name><name sortKey="Xie, Wei" sort="Xie, Wei" uniqKey="Xie W" first="Wei" last="Xie">Wei Xie</name><name sortKey="Zhang, Jing" sort="Zhang, Jing" uniqKey="Zhang J" first="Jing" last="Zhang">Jing Zhang</name></country></tree></affiliations></record>Pour manipuler ce 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