Thymoquinone affects hypoxia-inducible factor-1αexpression in pancreatic cancer cells via HSP90 and PI3K/AKT/mTOR pathways  

作　　者：Zhan-Xue Zhao Shuai Li Lin-Xun Liu 

机构地区：[1]Department of General Surgery,Qinghai Provincial People's Hospital,Xining 810007,Qinghai Province,China [2]Department of Clinical Pharmacy,The Affiliated Hospital of Qinghai University,Xining 810001,Qinghai Province,China

出　　处：《World Journal of Gastroenterology》2024年第21期2793-2816,共24页世界胃肠病学杂志（英文版）

基　　金：Supported by Health Commission of Qinghai Province,No.2021-wjzdx-18.

摘　　要：BACKGROUND 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-1α(HIF-1α)and PC have shown that HIF-1αaffects 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-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the mechanism.AIM To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1αexpression.METHODS 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(hTERTHPNE)cells.Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC cells.The effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.RESULTS 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-1αin PANC-1,AsPC-1,and BxPC-3 cells.TQ significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 cells.TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90,thus promoting its u

关 键 词：THYMOQUINONE Pancreatic cancer Hypoxia-inducible factor-1α PI3K/AKT/MTOR HSP90 

分 类 号：R735.9[医药卫生—肿瘤]