{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:07:52Z","timestamp":1788826072459,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009337","name":"Saitama Medical University","doi-asserted-by":"publisher","award":["16\u2010B\u20101\u201022"],"award-info":[{"award-number":["16\u2010B\u20101\u201022"]}],"id":[{"id":"10.13039\/501100009337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009337","name":"Saitama Medical University","doi-asserted-by":"publisher","award":["18\u2010B\u20101\u201019"],"award-info":[{"award-number":["18\u2010B\u20101\u201019"]}],"id":[{"id":"10.13039\/501100009337","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p><jats:bold>Background:<\/jats:bold> Pleural mesothelioma, a devastating asbestos\u2010associated malignancy, urgently requires a novel effective therapy. Heat shock protein 70 (HSP70), which is synthesized in the cell response to protein damage, is expected to be a new target for antitumor treatment. In addition to its well\u2010known protein refolding function, HSP70 regulates cell proliferation through different pathways, including PI3K\/AKT\/mTOR, and autophagy in malignant cells. In this study, we attempted to clarify the effects of VER\u2010155008, an HSP70 inhibitor, on pleural mesothelioma.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Human pleural mesothelioma cell lines 211H, H2452 and H28 were cultured with VER\u2010155008, and protein expression, cell proliferation, colony formation, cell cycle, synergistic effect with cisplatin, and autophagy induction were analyzed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In mesothelioma cell lines, VER\u2010155008 (5.0 \u03bcM or more) inhibited cell growth and colony formation, accompanied by G<jats:sub>1<\/jats:sub> cell cycle arrest. According to western blot analysis, VER\u2010155008 reduced p\u2010AKT expression. However, VER\u2010155008 failed to show a synergistic effect with cisplatin on cell growth. Mesothelioma cells transfected with the novel plasmid pMRX\u2010IP\u2010GFP\u2010LC3\u2010RFP\u2010LC3\u0394G, which was developed for the quantitative and statistical estimation of macroautophagy, showed enhanced macroautophagy upon treatment with VER\u2010155008 and gefitinib which is an EGFR\u2010tyrosine kinase inhibitor. In addition, fetal bovine serum deprivation induced macroautophagy was further enhanced by VER\u2010155008.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> On the basis of these results, functional HSP70 inhibition by VER\u2010155008 suppressed cell growth in pleural mesothelioma cells, accompanied by enhanced macroautophagy. HSP70 inhibition is thus expected to become a new strategy for treating mesothelioma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:bold>Significant findings of the study<\/jats:bold><\/jats:p><jats:p>In pleural mesothelioma cells, inhibition of HSP70 function by VER\u2010155008 suppressed cell proliferation accompanied by induction of autophagy which was synergistically enhanced under the starvation condition, whereas gefitinib, an EGFR\u2010TKI, did not show the same synergistic effect in autophagy.<\/jats:p><jats:p><jats:bold>What this study adds<\/jats:bold><\/jats:p><jats:p>The inhibition of HSP70 induced autophagy and suppressed cell proliferation in mesothelioma cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.13784","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T17:13:09Z","timestamp":1608052389000},"page":"491-503","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Functional inhibition of heat shock protein 70 by <scp>VER<\/scp>\u2010155008 suppresses pleural mesothelioma cell proliferation via an autophagy mechanism"],"prefix":"10.1111","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3138-0360","authenticated-orcid":false,"given":"Kosuke","family":"Sakai","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, Saitama Medical Center Saitama Medical University  Saitama Japan"},{"name":"Department of Pulmonary Medicine and Oncology Graduate School of Medicine, Nippon Medical School  Tokyo 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