Downregulation of BAG3 attenuates cisplatin resistance by inhibiting autophagy in human epithelial ovarian cancer cells
Identifieur interne : 000372 ( Pmc/Corpus ); précédent : 000371; suivant : 000373Downregulation of BAG3 attenuates cisplatin resistance by inhibiting autophagy in human epithelial ovarian cancer cells
Auteurs : Shuang Qiu ; Liang Sun ; Yan Zhang ; Shiyu HanSource :
- Oncology Letters [ 1792-1074 ] ; 2019.
Abstract
Epithelial ovarian cancer (EOC) is one of the most common malignant gynecological tumors. Interval cytoreductive surgery and cisplatin-based chemotherapy are the standard treatments. However, acquired resistance to cisplatin presents a major challenge for improving the overall survival and prognosis of patients. Recent evidence indicates that cytoprotective functions of autophagy in cancer cells is a potential mechanism for chemoresistance. The present study aimed to investigate the mechanisms responsible for cisplatin resistance in EOC cell lines. The results revealed that cisplatin activated autophagy, measured by an increase in the expression of LC3-II by western blot analysis, protecting ovarian cancer cells from cisplatin toxicity. The present study also identified Bcl-2-associated athanogene 3 (BAG3) as a novel autophagy regulator that serves a role in cisplatin resistance. Treatment with cisplatin was observed to enhance BAG3 expression in parental and cisplatin-resistant ovarian cancer cell lines, and the downregulation of BAG3 blocked cisplatin-induced autophagy, thereby increasing cisplatin sensitivity in the EOC cell lines. In conclusion, BAG3 attenuates cisplatin resistance by inhibiting autophagy, suggesting that downregulation of BAG3 may be a useful therapeutic strategy to overcome cisplatin resistance by preventing cytoprotective autophagy in EOC.
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DOI: 10.3892/ol.2019.10494
PubMed: 31423267
PubMed Central: 6607100
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Downregulation of BAG3 attenuates cisplatin resistance by inhibiting autophagy in human epithelial ovarian cancer cells</title><author><name sortKey="Qiu, Shuang" sort="Qiu, Shuang" uniqKey="Qiu S" first="Shuang" last="Qiu">Shuang Qiu</name><affiliation><nlm:aff id="af1-ol-0-0-10494">Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China</nlm:aff></affiliation></author><author><name sortKey="Sun, Liang" sort="Sun, Liang" uniqKey="Sun L" first="Liang" last="Sun">Liang Sun</name><affiliation><nlm:aff id="af2-ol-0-0-10494">Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China</nlm:aff></affiliation></author><author><name sortKey="Zhang, Yan" sort="Zhang, Yan" uniqKey="Zhang Y" first="Yan" last="Zhang">Yan Zhang</name><affiliation><nlm:aff id="af3-ol-0-0-10494">College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China</nlm:aff></affiliation></author><author><name sortKey="Han, Shiyu" sort="Han, Shiyu" uniqKey="Han S" first="Shiyu" last="Han">Shiyu Han</name><affiliation><nlm:aff id="af1-ol-0-0-10494">Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31423267</idno><idno type="pmc">6607100</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607100</idno><idno type="RBID">PMC:6607100</idno><idno type="doi">10.3892/ol.2019.10494</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000372</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000372</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Downregulation of BAG3 attenuates cisplatin resistance by inhibiting autophagy in human epithelial ovarian cancer cells</title><author><name sortKey="Qiu, Shuang" sort="Qiu, Shuang" uniqKey="Qiu S" first="Shuang" last="Qiu">Shuang Qiu</name><affiliation><nlm:aff id="af1-ol-0-0-10494">Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China</nlm:aff></affiliation></author><author><name sortKey="Sun, Liang" sort="Sun, Liang" uniqKey="Sun L" first="Liang" last="Sun">Liang Sun</name><affiliation><nlm:aff id="af2-ol-0-0-10494">Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China</nlm:aff></affiliation></author><author><name sortKey="Zhang, Yan" sort="Zhang, Yan" uniqKey="Zhang Y" first="Yan" last="Zhang">Yan Zhang</name><affiliation><nlm:aff id="af3-ol-0-0-10494">College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China</nlm:aff></affiliation></author><author><name sortKey="Han, Shiyu" sort="Han, Shiyu" uniqKey="Han S" first="Shiyu" last="Han">Shiyu Han</name><affiliation><nlm:aff id="af1-ol-0-0-10494">Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China</nlm:aff></affiliation></author></analytic><series><title level="j">Oncology Letters</title><idno type="ISSN">1792-1074</idno><idno type="eISSN">1792-1082</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>Epithelial ovarian cancer (EOC) is one of the most common malignant gynecological tumors. Interval cytoreductive surgery and cisplatin-based chemotherapy are the standard treatments. However, acquired resistance to cisplatin presents a major challenge for improving the overall survival and prognosis of patients. Recent evidence indicates that cytoprotective functions of autophagy in cancer cells is a potential mechanism for chemoresistance. The present study aimed to investigate the mechanisms responsible for cisplatin resistance in EOC cell lines. The results revealed that cisplatin activated autophagy, measured by an increase in the expression of LC3-II by western blot analysis, protecting ovarian cancer cells from cisplatin toxicity. The present study also identified Bcl-2-associated athanogene 3 (BAG3) as a novel autophagy regulator that serves a role in cisplatin resistance. Treatment with cisplatin was observed to enhance BAG3 expression in parental and cisplatin-resistant ovarian cancer cell lines, and the downregulation of BAG3 blocked cisplatin-induced autophagy, thereby increasing cisplatin sensitivity in the EOC cell lines. In conclusion, BAG3 attenuates cisplatin resistance by inhibiting autophagy, suggesting that downregulation of BAG3 may be a useful therapeutic strategy to overcome cisplatin resistance by preventing cytoprotective autophagy in EOC.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Oncol Lett</journal-id><journal-id journal-id-type="iso-abbrev">Oncol Lett</journal-id><journal-id journal-id-type="publisher-id">OL</journal-id><journal-title-group><journal-title>Oncology Letters</journal-title></journal-title-group><issn pub-type="ppub">1792-1074</issn><issn pub-type="epub">1792-1082</issn><publisher><publisher-name>D.A. Spandidos</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31423267</article-id><article-id pub-id-type="pmc">6607100</article-id><article-id pub-id-type="doi">10.3892/ol.2019.10494</article-id><article-id pub-id-type="publisher-id">OL-0-0-10494</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Downregulation of BAG3 attenuates cisplatin resistance by inhibiting autophagy in human epithelial ovarian cancer cells</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Qiu</surname><given-names>Shuang</given-names></name><xref ref-type="aff" rid="af1-ol-0-0-10494">1</xref><xref rid="c1-ol-0-0-10494" ref-type="corresp"></xref></contrib><contrib contrib-type="author"><name><surname>Sun</surname><given-names>Liang</given-names></name><xref ref-type="aff" rid="af2-ol-0-0-10494">2</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Yan</given-names></name><xref ref-type="aff" rid="af3-ol-0-0-10494">3</xref></contrib><contrib contrib-type="author"><name><surname>Han</surname><given-names>Shiyu</given-names></name><xref ref-type="aff" rid="af1-ol-0-0-10494">1</xref></contrib></contrib-group><aff id="af1-ol-0-0-10494"><label>1</label>Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China</aff><aff id="af2-ol-0-0-10494"><label>2</label>Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China</aff><aff id="af3-ol-0-0-10494"><label>3</label>College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China</aff><author-notes><corresp id="c1-ol-0-0-10494"><italic>Correspondence to</italic>: Dr Shuang Qiu, Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, 37 Yi Yuan Street, Harbin, Heilongjiang 150001, P.R. China, E-mail: <email>doctorqiushuang@hotmail.com</email></corresp></author-notes><pub-date pub-type="ppub"><month>8</month><year>2019</year></pub-date><pub-date pub-type="epub"><day>19</day><month>6</month><year>2019</year></pub-date><pub-date pub-type="pmc-release"><day>19</day><month>6</month><year>2019</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>18</volume><issue>2</issue><fpage>1969</fpage><lpage>1978</lpage><history><date date-type="received"><day>27</day><month>3</month><year>2018</year></date><date date-type="accepted"><day>05</day><month>4</month><year>2019</year></date></history><permissions><copyright-statement>Copyright © 2019, Spandidos Publications</copyright-statement><copyright-year>2019</copyright-year></permissions><abstract><p>Epithelial ovarian cancer (EOC) is one of the most common malignant gynecological tumors. Interval cytoreductive surgery and cisplatin-based chemotherapy are the standard treatments. However, acquired resistance to cisplatin presents a major challenge for improving the overall survival and prognosis of patients. Recent evidence indicates that cytoprotective functions of autophagy in cancer cells is a potential mechanism for chemoresistance. The present study aimed to investigate the mechanisms responsible for cisplatin resistance in EOC cell lines. The results revealed that cisplatin activated autophagy, measured by an increase in the expression of LC3-II by western blot analysis, protecting ovarian cancer cells from cisplatin toxicity. The present study also identified Bcl-2-associated athanogene 3 (BAG3) as a novel autophagy regulator that serves a role in cisplatin resistance. Treatment with cisplatin was observed to enhance BAG3 expression in parental and cisplatin-resistant ovarian cancer cell lines, and the downregulation of BAG3 blocked cisplatin-induced autophagy, thereby increasing cisplatin sensitivity in the EOC cell lines. In conclusion, BAG3 attenuates cisplatin resistance by inhibiting autophagy, suggesting that downregulation of BAG3 may be a useful therapeutic strategy to overcome cisplatin resistance by preventing cytoprotective autophagy in EOC.</p></abstract><kwd-group><kwd>BAG3</kwd><kwd>autophagy</kwd><kwd>ovarian cancer</kwd><kwd>cisplatin</kwd><kwd>chemoresistance</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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