{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:43:57Z","timestamp":1792842237850,"version":"4.5.0"},"reference-count":54,"publisher":"Baishideng Publishing Group Inc.","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Gastroenterol"],"abstract":"<jats:p>BACKGROUND<\/jats:p>\n          <jats:p>Pancreatic cancer (PC) is associated with some of the worst prognoses of all major cancers. Thymoquinone (TQ) has a long history in traditional medical practice and is known for its anti-cancer, anti-inflammatory, anti-fibrosis and antioxidant pharmacological activities. Recent studies on hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) and PC have shown that HIF-1\u03b1 affects the occurrence and development of PC in many aspects. In addition, TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1\u03b1. Therefore, we speculate whether TQ affects HIF-1\u03b1 expression in PC cells and explore the mechanism.<\/jats:p>\n          <jats:p>AIM<\/jats:p>\n          <jats:p>To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1\u03b1 expression.<\/jats:p>\n          <jats:p>METHODS<\/jats:p>\n          <jats:p>Cell counting kit-8 assay, Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity, migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial (hTERT-HPNE) cells. Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1\u03b1 mRNA and protein in PC cells. The effects of TQ on the HIF-1\u03b1 protein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.<\/jats:p>\n          <jats:p>RESULTS<\/jats:p>\n          <jats:p>TQ significantly inhibited proliferative activity, migration, and invasion ability and promoted apoptosis of PANC-1 cells; however, no significant effects on hTERT-HPNE cells were observed. TQ significantly reduced the mRNA and protein expression levels of HIF-1\u03b1 in PANC-1, AsPC-1, and BxPC-3 cells. TQ significantly inhibited the expression of the HIF-1\u03b1 initial expression pathway (PI3K\/AKT\/mTOR) related proteins, and promoted the ubiquitination degradation of the HIF-1\u03b1 protein in PANC-1 cells. TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1\u03b1 protein but affected the stability of the HIF-1\u03b1 protein by inhibiting the interaction between HIF-1\u03b1 and HSP90, thus promoting its ubiquitination degradation.<\/jats:p>\n          <jats:p>CONCLUSION<\/jats:p>\n          <jats:p>The regulatory mechanism of TQ on HIF-1\u03b1 protein expression in PC cells was mainly to promote the ubiquitination degradation of the HIF-1\u03b1 protein by inhibiting the interaction between HIF-1\u03b1 and HSP90; Secondly, TQ reduced the initial expression of HIF-1\u03b1 protein by inhibiting the PI3K\/AKT\/mTOR pathway.<\/jats:p>","DOI":"10.3748\/wjg.v30.i21.2793","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T07:14:27Z","timestamp":1717398867000},"page":"2793-2816","source":"Crossref","is-referenced-by-count":15,"title":["Thymoquinone affects hypoxia-inducible factor-1\u03b1 expression in pancreatic cancer cells via HSP90 and PI3K\/AKT\/mTOR pathways"],"prefix":"10.3748","volume":"30","author":[{"given":"Zhan-Xue","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Xun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2060","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-327736"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2019.05.001"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1272\/jnms.JNMS.2022_89-310"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(22)00501-0"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1032314"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00774"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nri2231"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1923"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10587"},{"key":"B11","doi-asserted-by":"crossref","unstructured":"Goldberger G, Arnaout MA, Aden D, Kay R, Rits M, Colten HR. 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