泮托拉唑对人胃腺癌细胞株SGC-7901缺氧诱导因子-1α表达的影响  

Effect of Pantoprazole on Hypoxia-inducible Factor-1α Expression in Human Gastric Adenocarcinoma Cell Line SGC-7901

作　　者：吴育美[1] 陈敏[1] 张斌[1] 杨德红[1] 邹晓平[1] 

机构地区：[1]南京大学医学院附属鼓楼医院消化科

出　　处：《胃肠病学》2010年第4期205-208,共4页Chinese Journal of Gastroenterology

摘　　要：背景：缺氧诱导因子-1α（HIF-1α）是一种与肿瘤的增殖、代谢、转移、耐药等密切相关的蛋白,以其为靶点进行干预对肿瘤治疗可能有效.研究显示泮托拉唑具有化疗增敏作用,关于其对HIF-1的影响,国内外鲜有相关报道.目的：观察泮托拉唑对人胃腺癌细胞株SGC-7901 HIF-1α表达和分布的影响,探讨其化疗增敏机制.方法：以不同浓度泮托拉唑（0～160μg/ml）处理SGC-7901细胞24 h,蛋白质印迹法检测HIF-1α蛋白表达,免疫荧光法观察HIF-1α蛋白的胞内分布.结果：泮托拉唑能显著抑制SGC-7901细胞的HIF-1α蛋白表达,抑制作用与药物浓度有关且存在最适浓度（10μg/ml）;在一定浓度下（20μg/ml）,洋托拉唑还能抑制HIF-1α蛋白的核周浓集.结论：泮托拉唑能显著抑制SGC-7901细胞的HIF-1a表达,并在一定程度上影响其胞内分布,这可能是其化疗增敏作用的机制之一.Background： Hypoxia-inducible factor-1α （HIF-1α） plays important role in proliferation, metabolism, metastasis and drug resistance of malignant tumors, thus it might be an effective target for cancer therapy. It has been reported that pantoprazole increased the sensitivity of cancer cells to cytotoxic agents; however, there are few studies focusing on its effect on HIF-1. Aims： To investigate the effect of pantoprazole on expression and distribution of HIF-1α in human gastric adenoearcinoma cell line SGC-7901 and the mechanism of its chemosensitizing effect. Methods： The HIF-1α protein expression in SGC-7901 cells after treatment with pantoprazole at different concentrations （0-160 μg/ml） for 24 hours was determined by Western blotting, and the intracellular distribution of HIF-1α protein was assessed by immunofluorescence assay. Results： Pantoprazole pretreatment induced a marked decrease in the expression of HIF-1α protein in SGC-7901 cells, the inhibitory effect was related to the concentration of the drug and the optimizing concentration was 10 μg/ml. Pantoprazole pretreatment at a concentration of 20μg/ml also inhibited the perinuclear accumulation of HIF-1α protein. Conclusions： Pantoprazole inhibits HIF-1α expression and affects its intracellular distribution in SGC-7901 cells, which might be one of the mechanisms of its chemosensitizing effect on cancer cells.

关 键 词：胃肿瘤 抗药性 肿瘤 泮托拉唑 缺氧诱导因子1α亚基 

分 类 号：R735.2[医药卫生—肿瘤]