CS-PEI/Beclin-siRNA Downregulate Multidrug Resistance Proteins and Increase Paclitaxel Therapeutic Efficacy against NSCLC
Identifieur interne : 000831 ( Ncbi/Merge ); précédent : 000830; suivant : 000832CS-PEI/Beclin-siRNA Downregulate Multidrug Resistance Proteins and Increase Paclitaxel Therapeutic Efficacy against NSCLC
Auteurs : Wangta Liu [Taïwan] ; Yu-Lun Lo [Taïwan] ; Chin Hsu [Taïwan] ; Yi-Ting Wu [Taïwan] ; Zi-Xian Liao [Taïwan] ; Wen-Jeng Wu [Taïwan] ; Yi-Jou Chen [Taïwan] ; Chieh Kao [Taïwan] ; Chien-Chih Chiu [Taïwan] ; Li-Fang Wang [Taïwan]Source :
- Molecular Therapy. Nucleic Acids [ 2162-2531 ] ; 2019.
Abstract
Paclitaxel (PTX) is a widely used chemotherapy drug; however, frequent use causes multidrug resistance (MDR), which limits the utility of PTX against advanced non-small-cell lung cancer (NSCLC). PTX-resistant subline (NCI-H23-TXR) was established
Url:
DOI: 10.1016/j.omtn.2019.06.017
PubMed: 31336235
PubMed Central: 6656922
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wicri:level="1"><nlm:aff id="aff1">Department of Biotechnology, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Biotechnology, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807</wicri:regionArea><wicri:noRegion>Kaohsiung 807</wicri:noRegion></affiliation></author><author><name sortKey="Lo, Yu Lun" sort="Lo, Yu Lun" uniqKey="Lo Y" first="Yu-Lun" last="Lo">Yu-Lun Lo</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Medicinal and Applied Chemistry, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Medicinal and Applied Chemistry, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807</wicri:regionArea><wicri:noRegion>Kaohsiung 807</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Physiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Physiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807</wicri:regionArea><wicri:noRegion>Kaohsiung 807</wicri:noRegion></affiliation></author><author><name sortKey="Hsu, Chin" sort="Hsu, Chin" uniqKey="Hsu C" first="Chin" last="Hsu">Chin Hsu</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Physiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Physiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807</wicri:regionArea><wicri:noRegion>Kaohsiung 807</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Medical Research, Kaohsiung Medical 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id="aff5">Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 804, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 804</wicri:regionArea><wicri:noRegion>Kaohsiung 804</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Wen Jeng" sort="Wu, Wen Jeng" uniqKey="Wu W" first="Wen-Jeng" last="Wu">Wen-Jeng Wu</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807</wicri:regionArea><wicri:noRegion>Kaohsiung 807</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807</wicri:regionArea><wicri:noRegion>Kaohsiung 807</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yi Jou" sort="Chen, Yi Jou" uniqKey="Chen Y" first="Yi-Jou" last="Chen">Yi-Jou Chen</name><affiliation wicri:level="1"><nlm:aff id="aff7">School of Medicine, Chang Guan University, Taoyuan City 33302, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>School of Medicine, Chang Guan University, Taoyuan City 33302</wicri:regionArea><wicri:noRegion>Taoyuan City 33302</wicri:noRegion></affiliation></author><author><name sortKey="Kao, Chieh" sort="Kao, Chieh" uniqKey="Kao C" first="Chieh" last="Kao">Chieh Kao</name><affiliation wicri:level="1"><nlm:aff id="aff8">School of Medicine for International Students, I-Shou University, Kaohsiung 82445, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>School of Medicine for International Students, I-Shou University, Kaohsiung 82445</wicri:regionArea><wicri:noRegion>Kaohsiung 82445</wicri:noRegion></affiliation></author><author><name sortKey="Chiu, Chien Chih" sort="Chiu, Chien Chih" uniqKey="Chiu C" first="Chien-Chih" last="Chiu">Chien-Chih Chiu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Biotechnology, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Biotechnology, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807</wicri:regionArea><wicri:noRegion>Kaohsiung 807</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807</wicri:regionArea><wicri:noRegion>Kaohsiung 807</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Li Fang" sort="Wang, Li Fang" uniqKey="Wang L" first="Li-Fang" last="Wang">Li-Fang Wang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Medicinal and Applied Chemistry, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Medicinal and Applied Chemistry, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807</wicri:regionArea><wicri:noRegion>Kaohsiung 807</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807</wicri:regionArea><wicri:noRegion>Kaohsiung 807</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 804, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 804</wicri:regionArea><wicri:noRegion>Kaohsiung 804</wicri:noRegion></affiliation></author></analytic><series><title level="j">Molecular Therapy. Nucleic Acids</title><idno type="eISSN">2162-2531</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>Paclitaxel (PTX) is a widely used chemotherapy drug; however, frequent use causes multidrug resistance (MDR), which limits the utility of PTX against advanced non-small-cell lung cancer (NSCLC). PTX-resistant subline (NCI-H23-TXR) was established <italic>in vitro</italic> by exposing NCI-H23 cells to gradually increased concentrations of PTX in culture medium. Distinct Beclin expression of autophagy level was observed between resistant NCI-H23-TXR and parental NCI-H23 cells. Beclin-small interfering RNA (siRNA) was selected to restore sensitivity of PTX against NCI-H23-TXR. Chondroitin sulfate-polyethylenimine (CS-PEI) was constructed for delivery and protection of Beclin-siRNA. To delineate the underlying molecular mechanism of Beclin knockdown, we analyzed different MDR expression proteins of two cells using western blot, and the corresponding genes were confirmed by real-time PCR. Compared with NCI-H23, NCI-H23-TXR had higher expression levels in P-glycoprotein (P-gp) and multidrug resistance protein 7 (ABCC10). Knockdown of Beclin simultaneously inhibited P-gp and ABCC10, and renewed the sensitivity of PTX against NCI-H23-TXR. Research on zebrafish embryos revealed that tumor sizes decreased in NCI-H23 tumor xenografts but remained intact in NCI-H23-TXR tumor xenografts as zebrafish were treated with 1 μg/mL PTX. In contrast, the tumor sizes decreased in NCI-H23-TXR tumor xenografts with zebrafish pre-transfected with CS-PEI/Beclin-siRNA followed by the same treatment of PTX. The role of autophagy was associated with MDR development. This study paves the way for a new avenue of PTX in MDR-related lung cancer therapy using CS-PEI as a gene delivery carrier.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Yeh, J J" uniqKey="Yeh J">J.J. Yeh</name></author><author><name sortKey="Hsu, W H" uniqKey="Hsu W">W.H. Hsu</name></author><author><name sortKey="Wang, J J" uniqKey="Wang J">J.J. Wang</name></author><author><name sortKey="Ho, S T" uniqKey="Ho S">S.T. Ho</name></author><author><name sortKey="Kao, A" uniqKey="Kao A">A. Kao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Y D" uniqKey="Kim Y">Y.D. Kim</name></author><author><name sortKey="Park, T E" uniqKey="Park T">T.E. Park</name></author><author><name sortKey="Singh, B" uniqKey="Singh B">B. Singh</name></author><author><name sortKey="Maharjan, S" uniqKey="Maharjan S">S. Maharjan</name></author><author><name sortKey="Choi, Y J" uniqKey="Choi Y">Y.J. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Mol Ther Nucleic Acids</journal-id><journal-id journal-id-type="iso-abbrev">Mol Ther Nucleic Acids</journal-id><journal-title-group><journal-title>Molecular Therapy. Nucleic Acids</journal-title></journal-title-group><issn pub-type="epub">2162-2531</issn><publisher><publisher-name>American Society of Gene & Cell Therapy</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31336235</article-id><article-id pub-id-type="pmc">6656922</article-id><article-id pub-id-type="publisher-id">S2162-2531(19)30180-5</article-id><article-id pub-id-type="doi">10.1016/j.omtn.2019.06.017</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>CS-PEI/Beclin-siRNA Downregulate Multidrug Resistance Proteins and Increase Paclitaxel Therapeutic Efficacy against NSCLC</article-title></title-group><contrib-group><contrib contrib-type="author" id="au1"><name><surname>Liu</surname><given-names>Wangta</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="fn1" ref-type="fn">9</xref></contrib><contrib contrib-type="author" id="au2"><name><surname>Lo</surname><given-names>Yu-Lun</given-names></name><xref rid="aff2" ref-type="aff">2</xref><xref rid="aff3" ref-type="aff">3</xref><xref rid="fn1" ref-type="fn">9</xref></contrib><contrib contrib-type="author" id="au3"><name><surname>Hsu</surname><given-names>Chin</given-names></name><xref rid="aff3" ref-type="aff">3</xref><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author" id="au4"><name><surname>Wu</surname><given-names>Yi-Ting</given-names></name><xref rid="aff2" ref-type="aff">2</xref></contrib><contrib contrib-type="author" id="au5"><name><surname>Liao</surname><given-names>Zi-Xian</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author" id="au6"><name><surname>Wu</surname><given-names>Wen-Jeng</given-names></name><xref rid="aff4" ref-type="aff">4</xref><xref rid="aff6" ref-type="aff">6</xref></contrib><contrib contrib-type="author" id="au7"><name><surname>Chen</surname><given-names>Yi-Jou</given-names></name><xref rid="aff7" ref-type="aff">7</xref></contrib><contrib contrib-type="author" id="au8"><name><surname>Kao</surname><given-names>Chieh</given-names></name><xref rid="aff8" ref-type="aff">8</xref></contrib><contrib contrib-type="author" id="au9"><name><surname>Chiu</surname><given-names>Chien-Chih</given-names></name><email>cchiu@kmu.edu.tw</email><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff4" ref-type="aff">4</xref><xref rid="cor2" ref-type="corresp">∗∗</xref></contrib><contrib contrib-type="author" id="au10"><name><surname>Wang</surname><given-names>Li-Fang</given-names></name><email>lfwang@kmu.edu.tw</email><xref rid="aff2" ref-type="aff">2</xref><xref rid="aff4" ref-type="aff">4</xref><xref rid="aff5" ref-type="aff">5</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Department of Biotechnology, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan</aff><aff id="aff2"><label>2</label>Department of Medicinal and Applied Chemistry, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan</aff><aff id="aff3"><label>3</label>Department of Physiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan</aff><aff id="aff4"><label>4</label>Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan</aff><aff id="aff5"><label>5</label>Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 804, Taiwan</aff><aff id="aff6"><label>6</label>Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan</aff><aff id="aff7"><label>7</label>School of Medicine, Chang Guan University, Taoyuan City 33302, Taiwan</aff><aff id="aff8"><label>8</label>School of Medicine for International Students, I-Shou University, Kaohsiung 82445, Taiwan</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author: Li-Fang Wang, Department of Medicinal and Applied Chemistry, College of Life Sciences, Kaohsiung Medical University, 100, Shih-Chuan 1<sup>st</sup> Rd, Kaohsiung City 807, Taiwan. <email>lfwang@kmu.edu.tw</email></corresp><corresp id="cor2"><label>∗∗</label>Corresponding author: Chien-Chih Chiu, Department of Biotechnology, College of Life Sciences, Kaohsiung Medical University, 100, Shih-Chuan 1<sup>st</sup> Rd, Kaohsiung City 807, Taiwan. <email>cchiu@kmu.edu.tw</email></corresp><fn id="fn1"><label>9</label><p id="ntpara0010">These authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="pmc-release"><day>29</day><month>6</month><year>2019</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="collection"><day>06</day><month>9</month><year>2019</year></pub-date><pub-date pub-type="epub"><day>29</day><month>6</month><year>2019</year></pub-date><volume>17</volume><fpage>477</fpage><lpage>490</lpage><history><date date-type="received"><day>20</day><month>3</month><year>2019</year></date><date date-type="accepted"><day>18</day><month>6</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 The Authors</copyright-statement><copyright-year>2019</copyright-year><license license-type="CC BY-NC-ND" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/"><license-p>This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).</license-p></license></permissions><abstract id="abs0010"><p>Paclitaxel (PTX) is a widely used chemotherapy drug; however, frequent use causes multidrug resistance (MDR), which limits the utility of PTX against advanced non-small-cell lung cancer (NSCLC). PTX-resistant subline (NCI-H23-TXR) was established <italic>in vitro</italic> by exposing NCI-H23 cells to gradually increased concentrations of PTX in culture medium. Distinct Beclin expression of autophagy level was observed between resistant NCI-H23-TXR and parental NCI-H23 cells. Beclin-small interfering RNA (siRNA) was selected to restore sensitivity of PTX against NCI-H23-TXR. Chondroitin sulfate-polyethylenimine (CS-PEI) was constructed for delivery and protection of Beclin-siRNA. To delineate the underlying molecular mechanism of Beclin knockdown, we analyzed different MDR expression proteins of two cells using western blot, and the corresponding genes were confirmed by real-time PCR. Compared with NCI-H23, NCI-H23-TXR had higher expression levels in P-glycoprotein (P-gp) and multidrug resistance protein 7 (ABCC10). Knockdown of Beclin simultaneously inhibited P-gp and ABCC10, and renewed the sensitivity of PTX against NCI-H23-TXR. Research on zebrafish embryos revealed that tumor sizes decreased in NCI-H23 tumor xenografts but remained intact in NCI-H23-TXR tumor xenografts as zebrafish were treated with 1 μg/mL PTX. In contrast, the tumor sizes decreased in NCI-H23-TXR tumor xenografts with zebrafish pre-transfected with CS-PEI/Beclin-siRNA followed by the same treatment of PTX. The role of autophagy was associated with MDR development. This study paves the way for a new avenue of PTX in MDR-related lung cancer therapy using CS-PEI as a gene delivery carrier.</p></abstract><kwd-group id="kwrds0010"><title>Keywords</title><kwd>autophagy</kwd><kwd>Beclin-siRNA</kwd><kwd>multidrug resistance</kwd><kwd>MDR</kwd><kwd>non-viral gene delivery vector</kwd><kwd>paclitaxel</kwd><kwd>PTX</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>Taïwan</li></country></list><tree><country name="Taïwan"><noRegion><name sortKey="Liu, Wangta" sort="Liu, Wangta" uniqKey="Liu W" first="Wangta" last="Liu">Wangta Liu</name></noRegion><name sortKey="Chen, Yi Jou" sort="Chen, Yi Jou" uniqKey="Chen Y" first="Yi-Jou" last="Chen">Yi-Jou Chen</name><name sortKey="Chiu, Chien Chih" sort="Chiu, Chien Chih" uniqKey="Chiu C" first="Chien-Chih" last="Chiu">Chien-Chih Chiu</name><name sortKey="Chiu, Chien Chih" sort="Chiu, Chien Chih" uniqKey="Chiu C" first="Chien-Chih" last="Chiu">Chien-Chih Chiu</name><name sortKey="Hsu, Chin" sort="Hsu, Chin" uniqKey="Hsu C" first="Chin" last="Hsu">Chin Hsu</name><name sortKey="Hsu, Chin" sort="Hsu, Chin" uniqKey="Hsu C" first="Chin" last="Hsu">Chin Hsu</name><name sortKey="Kao, Chieh" sort="Kao, Chieh" uniqKey="Kao C" first="Chieh" last="Kao">Chieh Kao</name><name sortKey="Liao, Zi Xian" sort="Liao, Zi Xian" uniqKey="Liao Z" first="Zi-Xian" last="Liao">Zi-Xian Liao</name><name sortKey="Lo, Yu Lun" sort="Lo, Yu Lun" uniqKey="Lo Y" first="Yu-Lun" last="Lo">Yu-Lun Lo</name><name sortKey="Lo, Yu Lun" sort="Lo, Yu Lun" uniqKey="Lo Y" first="Yu-Lun" last="Lo">Yu-Lun Lo</name><name sortKey="Wang, Li Fang" sort="Wang, Li Fang" uniqKey="Wang L" first="Li-Fang" last="Wang">Li-Fang Wang</name><name sortKey="Wang, Li Fang" sort="Wang, Li Fang" uniqKey="Wang L" first="Li-Fang" last="Wang">Li-Fang Wang</name><name sortKey="Wang, Li Fang" sort="Wang, Li Fang" uniqKey="Wang L" first="Li-Fang" last="Wang">Li-Fang Wang</name><name sortKey="Wu, Wen Jeng" sort="Wu, Wen Jeng" uniqKey="Wu W" first="Wen-Jeng" last="Wu">Wen-Jeng Wu</name><name sortKey="Wu, Wen Jeng" sort="Wu, Wen Jeng" uniqKey="Wu W" first="Wen-Jeng" last="Wu">Wen-Jeng Wu</name><name sortKey="Wu, Yi Ting" sort="Wu, Yi Ting" uniqKey="Wu Y" first="Yi-Ting" last="Wu">Yi-Ting Wu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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