{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:51:07Z","timestamp":1792122667540,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A hypoxic microenvironment results in significantly elevated hypoxia\u2010inducible factor\u20101 (HIF\u20101) level in pancreatic cancer. HIF\u20101 functions to maintain the survival of cancer cells. The present study was performed to investigate whether inhibition of HIF\u20101\u03b1 expression was involved in the in vitro antitumor effect of rhein in pancreatic cancer cells and to explore the underlying mechanism. sh\u2010RNA knockout technique and western blotting were used to investigate the role of HIF\u20101\u03b1 in autophagy activation in MiaPaCa\u20102 and PANC\u20101 cells. The survival and glycolysis were assessed using MTT assay and colorimetric kits, respectively. Apoptosis was evaluated by detecting the levels of apoptosis\u2010related proteins using western blotting. Among the five pancreatic cancer cell lines, MiaPaCa\u20102 and PANC\u20101 cells were more sensitive to hypoxia\u2010induced autophagy. HIF\u20101\u03b1 regulated hypoxia\u2010induced autophagy in MiaPaCa\u20102 and PANC\u20101 cells. Treatment with rhein inhibited the survival and suppressed glycolysis in MiaPaCa\u20102 and PANC\u20101 cells exposed to hypoxia. Bafilomycin A1 enhanced the suppressive effects of rhein on cell survival and glycolysis under hypoxia. Treatment with rhein, but not bafilomycin A1, significantly reduced HIF\u20101\u03b1 expression. In conclusion, inhibition of HIF\u20101\u03b1\u2010mediated autophagy enhances the in vitro antitumor activity of rhein in pancreatic cancer cells under hypoxia.<\/jats:p>","DOI":"10.1002\/jat.4365","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T22:53:12Z","timestamp":1658271192000},"page":"1937-1947","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Inhibition of hypoxia\u2010induced HIF\u20101\u03b1\u2010mediated autophagy enhances the in vitro antitumor activity of rhein in pancreatic cancer cells"],"prefix":"10.1002","volume":"42","author":[{"given":"Chuanshan","family":"Yao","sequence":"first","affiliation":[{"name":"The Medical School Nankai University  Tianjin China"},{"name":"Department of Oncology Nanyang First People's Hospital  Henan 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