西罗莫司对肝癌HepG2细胞的增殖及mTOR、HIF-1α的抑制作用  

Sirolimus inhibits cell proliferation and downregulates mTOR and HIF-1α expression in human hepatic carcinoma HepG2 cells

作　　者：王渝[1] 熊晶[1] 程恒辉[1] 周晟[1] 赵秋[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院病理科,湖北省武汉市430030 [2]华中科技大学同济医学院附属同济医院消化内科,湖北省武汉市430030

出　　处：《世界华人消化杂志》2009年第31期3241-3243,共3页World Chinese Journal of Digestology

摘　　要：目的:观察西罗莫司对体外培养的肝癌HepG2细胞增殖及mTOR、HIF-1α基因的抑制作用,探讨以mTOR为靶点治疗肝癌可能的细胞内信号转导机制.方法:缺氧培养HepG2细胞,外源性给予不同浓度的西罗莫司(0.1-1000nmol/L)刺激细胞24h,MTT法检测不同浓度药物对肝癌细胞增殖的影响.Western blot法检测药物刺激后HepG2细胞内mTOR和HIF-1α蛋白的表达.结果:西罗莫司可显著抑制肝癌细胞HepG2的增殖,其抑制率随药物浓度的增加而上升(均P<0.05).在西罗莫司的干预下,HepG2细胞中mTOR和HIF-1α蛋白的表达水平显著下降,实验组与对照组比较,差异有统计学意义(P<0.05).结论:在缺氧条件下,西罗莫司可通过mTOR信号转导途径下调肝癌HepG2细胞内HIF-1α蛋白表达,诱导细胞凋亡,这可能是西罗莫司发挥抗肿瘤效应的机制之一.AIM： To investigate the inhibitory effects of sirolimus on cell proliferation and mammalian target of rapamycin （mTOR） and hypoxia inducible factor-1α （HIF-1α） expression in human hepatic carcionoma HepG2 cells, and explore the potential mechanisms involved in the therapeutic effects of sirolimus against hepatic carcinoma. METHODS： HepG2 cells were cultured under hypoxic conditions. Different concentrations of sirolimus （0.1-1000 nmol/L） were incubatedwith HepG2 cells for 24 hours. Cell proliferation was measured by methyl thiazolyl tetrazolium （MTT） assay. The expression of mTOR and HIF- 1α proteins was determined by Western blot. RESULTS： Sirolimus could significantly inhibit the proliferation of HepG2 cells in a concentration-dependent manner （all P 〈 0.05）. The expression levels of mTOR and HIF-1α proteins were significantly lower in sirolimus-treated HepG2 cells than in untreated cells （both P 〈 0.05）. CONCLUSION： Sirolimus exerts anticancer activity possibly by downregulating HIF-1α expression and inducing apoptosis in HepG2 cells under hypoxia conditions via a mechanim dependent on the mTOR signaling pathway.

关 键 词：西罗莫司 肝癌 哺乳动物雷帕霉素靶蛋白 缺氧诱导因子-1Α 

分 类 号：R735.7[医药卫生—肿瘤] R273.57[医药卫生—临床医学]