LW6 enhances chemosensitivity to gemcitabine and inhibits autophagic flux in pancreatic cancer
Identifieur interne : 000643 ( Pmc/Curation ); précédent : 000642; suivant : 000644LW6 enhances chemosensitivity to gemcitabine and inhibits autophagic flux in pancreatic cancer
Auteurs : Xianbin Zhang [Allemagne] ; Simone Kumstel [Allemagne] ; Ke Jiang [République populaire de Chine] ; Songshu Meng [République populaire de Chine] ; Peng Gong [République populaire de Chine] ; Brigitte Vollmar [Allemagne] ; Dietmar Zechner [Allemagne]Source :
- Journal of Advanced Research [ 2090-1232 ] ; 2019.
Abstract
Url:
DOI: 10.1016/j.jare.2019.04.006
PubMed: 31193017
PubMed Central: 6514270
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PMC:6514270Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">LW6 enhances chemosensitivity to gemcitabine and inhibits autophagic flux in pancreatic cancer</title><author><name sortKey="Zhang, Xianbin" sort="Zhang, Xianbin" uniqKey="Zhang X" first="Xianbin" last="Zhang">Xianbin Zhang</name><affiliation wicri:level="1"><nlm:aff id="af005">Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18059 Rostock, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18059 Rostock</wicri:regionArea></affiliation></author><author><name sortKey="Kumstel, Simone" sort="Kumstel, Simone" uniqKey="Kumstel S" first="Simone" last="Kumstel">Simone Kumstel</name><affiliation wicri:level="1"><nlm:aff id="af005">Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18059 Rostock, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18059 Rostock</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Ke" sort="Jiang, Ke" uniqKey="Jiang K" first="Ke" last="Jiang">Ke Jiang</name><affiliation wicri:level="1"><nlm:aff id="af010">Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Lvshun South Road 9W, 116044 Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Lvshun South Road 9W, 116044 Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Meng, Songshu" sort="Meng, Songshu" uniqKey="Meng S" first="Songshu" last="Meng">Songshu Meng</name><affiliation wicri:level="1"><nlm:aff id="af010">Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Lvshun South Road 9W, 116044 Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Lvshun South Road 9W, 116044 Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Gong, Peng" sort="Gong, Peng" uniqKey="Gong P" first="Peng" last="Gong">Peng Gong</name><affiliation wicri:level="1"><nlm:aff id="af015">Department of General Surgery, Shenzhen University General Hospital, Xueyuan Road 1098, 518055 Shenzhen, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of General Surgery, Shenzhen University General Hospital, Xueyuan Road 1098, 518055 Shenzhen</wicri:regionArea></affiliation></author><author><name sortKey="Vollmar, Brigitte" sort="Vollmar, Brigitte" uniqKey="Vollmar B" first="Brigitte" last="Vollmar">Brigitte Vollmar</name><affiliation wicri:level="1"><nlm:aff id="af005">Institute for Experimental Surgery, Rostock University 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University Medical Center, Schillingallee 69a, 18059 Rostock</wicri:regionArea></affiliation></author><author><name sortKey="Kumstel, Simone" sort="Kumstel, Simone" uniqKey="Kumstel S" first="Simone" last="Kumstel">Simone Kumstel</name><affiliation wicri:level="1"><nlm:aff id="af005">Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18059 Rostock, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18059 Rostock</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Ke" sort="Jiang, Ke" uniqKey="Jiang K" first="Ke" last="Jiang">Ke Jiang</name><affiliation wicri:level="1"><nlm:aff id="af010">Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Lvshun South Road 9W, 116044 Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Lvshun South Road 9W, 116044 Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Meng, Songshu" sort="Meng, Songshu" uniqKey="Meng S" first="Songshu" last="Meng">Songshu Meng</name><affiliation wicri:level="1"><nlm:aff id="af010">Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Lvshun South Road 9W, 116044 Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Lvshun South Road 9W, 116044 Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Gong, Peng" sort="Gong, Peng" uniqKey="Gong P" first="Peng" last="Gong">Peng Gong</name><affiliation wicri:level="1"><nlm:aff id="af015">Department of General Surgery, Shenzhen University General Hospital, Xueyuan Road 1098, 518055 Shenzhen, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of General Surgery, Shenzhen University General Hospital, Xueyuan Road 1098, 518055 Shenzhen</wicri:regionArea></affiliation></author><author><name sortKey="Vollmar, Brigitte" sort="Vollmar, Brigitte" uniqKey="Vollmar B" first="Brigitte" last="Vollmar">Brigitte Vollmar</name><affiliation wicri:level="1"><nlm:aff id="af005">Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18059 Rostock, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18059 Rostock</wicri:regionArea></affiliation></author><author><name sortKey="Zechner, Dietmar" sort="Zechner, Dietmar" uniqKey="Zechner D" first="Dietmar" last="Zechner">Dietmar Zechner</name><affiliation wicri:level="1"><nlm:aff id="af005">Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18059 Rostock, 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Adv Res</journal-id><journal-id journal-id-type="iso-abbrev">J Adv Res</journal-id><journal-title-group><journal-title>Journal of Advanced Research</journal-title></journal-title-group><issn pub-type="ppub">2090-1232</issn><issn pub-type="epub">2090-1224</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31193017</article-id><article-id pub-id-type="pmc">6514270</article-id><article-id pub-id-type="publisher-id">S2090-1232(19)30084-0</article-id><article-id pub-id-type="doi">10.1016/j.jare.2019.04.006</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>LW6 enhances chemosensitivity to gemcitabine and inhibits autophagic flux in pancreatic cancer</article-title></title-group><contrib-group><contrib contrib-type="author" id="au005"><name><surname>Zhang</surname><given-names>Xianbin</given-names></name><email>zhangxianbin@hotmail.com</email><xref rid="af005" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">⁎</xref></contrib><contrib contrib-type="author" id="au010"><name><surname>Kumstel</surname><given-names>Simone</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au015"><name><surname>Jiang</surname><given-names>Ke</given-names></name><xref rid="af010" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au020"><name><surname>Meng</surname><given-names>Songshu</given-names></name><xref rid="af010" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au025"><name><surname>Gong</surname><given-names>Peng</given-names></name><xref rid="af015" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au030"><name><surname>Vollmar</surname><given-names>Brigitte</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au035"><name><surname>Zechner</surname><given-names>Dietmar</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib></contrib-group><aff id="af005"><label>a</label>Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18059 Rostock, Germany</aff><aff id="af010"><label>b</label>Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Lvshun South Road 9W, 116044 Dalian, China</aff><aff id="af015"><label>c</label>Department of General Surgery, Shenzhen University General Hospital, Xueyuan Road 1098, 518055 Shenzhen, China</aff><author-notes><corresp id="cor1"><label>⁎</label>Corresponding author. <email>zhangxianbin@hotmail.com</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>24</day><month>4</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"><month>11</month><year>2019</year></pub-date><pub-date pub-type="epub"><day>24</day><month>4</month><year>2019</year></pub-date><volume>20</volume><fpage>9</fpage><lpage>21</lpage><history><date date-type="received"><day>8</day><month>11</month><year>2018</year></date><date date-type="rev-recd"><day>18</day><month>4</month><year>2019</year></date><date date-type="accepted"><day>19</day><month>4</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 abstract-type="graphical" id="ab005"><title>Graphical abstract</title><fig id="f0060" position="anchor"><graphic xlink:href="ga1"></graphic></fig></abstract><abstract abstract-type="author-highlights" id="ab010"><title>Highlights</title><p><list list-type="simple" id="l0005"><list-item id="o0005"><label>•</label><p id="p0005">LW6 inhibits proliferation and induces cell death in pancreatic cancer cells.</p></list-item><list-item id="o0010"><label>•</label><p id="p0010">LW6 improves the anti-proliferation efficacy of gemcitabine.</p></list-item><list-item id="o0015"><label>•</label><p id="p0015">LW6 enhances gemcitabine-induced cell death.</p></list-item><list-item id="o0020"><label>•</label><p id="p0020">LW6 in combination with gemcitabine decreases tumor weight.</p></list-item><list-item id="o0025"><label>•</label><p id="p0025">LW6 inhibits autophagic flux.</p></list-item></list></p></abstract><abstract id="ab015"><p>The efficacy of gemcitabine therapy is often insufficient for the treatment of pancreatic cancer. The current study demonstrated that LW6, a chemical inhibitor of hypoxia-inducible factor 1α, is a promising drug for enhancing the chemosensitivity to gemcitabine. LW6 monotherapy and the combination therapy of LW6 plus gemcitabine significantly inhibited cell proliferation and enhanced cell death in pancreatic cancer cells. This combination therapy also significantly reduced the tumor weight in a syngeneic orthotopic pancreatic carcinoma model without causing toxic side effects. In addition, this study provides insight into the mechanism of how LW6 interferes with the pathophysiology of pancreatic cancer. The results revealed that LW6 inhibited autophagic flux, which is defined by the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and p62/SQSTM1. Moreover, these results were verified by the analysis of a tandem RFP-GFP-tagged LC3 protein. Thence, for the first time, these data demonstrate that LW6 enhances the anti-tumor effects of gemcitabine and inhibits autophagic flux. This suggests that the combination therapy of LW6 plus gemcitabine may be a novel therapeutic strategy for pancreatic cancer patients.</p></abstract><kwd-group id="kg005"><title>Keywords</title><kwd>LW6</kwd><kwd>Gemcitabine</kwd><kwd>Pancreatic cancer</kwd><kwd>Autophagy</kwd><kwd>Combination therapy</kwd></kwd-group><kwd-group id="kg010"><title>Abbreviations</title><kwd>LC3, microtubule-associated protein 1 light chain 3</kwd><kwd>p62, p62/SQSTM1</kwd><kwd>CQ, chloroquine</kwd><kwd>BrdU, 5-bromo-2′-deoxyuridine</kwd><kwd>3-MA, 3-methyladenine</kwd><kwd>ATCC, American Type Culture Collection</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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