索拉菲尼增强TRAIL诱导人肝癌细胞凋亡的作用及机制探讨  

Sorafenib Enhanced Apoptosis of Hepatocellular Carcinoma Cells Induced by TRAIL

作　　者：全梅芳[1] 钟志宏[1] 杨军[2] 

机构地区：[1]湖南师范大学医学院,湖南长沙410013 [2]中南大学湘雅三医院病理科,湖南长沙410006

出　　处：《肿瘤药学》2012年第3期169-172,共4页Anti-Tumor Pharmacy

基　　金：湖南省卫生厅医药科研项目(B2010-030)

摘　　要：目的观察索拉菲尼(Sorafenib)是否能增强肿瘤坏死因子相关凋亡诱导配体(TRAIL)诱导人肝癌细胞凋亡并探讨其作用机制。方法体外培养人肝癌HepG2细胞,MTT法测定细胞增殖活性,碘化丙啶(PI)染色流式细胞术(FCM)和细胞凋亡ELISA检测试剂盒检测细胞凋亡,Western blotting分析Mcl-1的表达。结果索拉菲尼具有增强TRAIL诱导人肝癌HepG2细胞凋亡的作用,并呈剂量和时间依赖的方式抑制Mcl-1的表达。Mcl-1过表达能抑制索拉菲尼增强TRAIL诱导HepG2细胞凋亡的作用。结论索拉菲尼通过抑制Mcl-1的蛋白表达增强TRAIL诱导人肝癌细胞凋亡的作用。Objective To investigate whether Sorafenib could enhance the tumor necrosis factor-related apoptosis inducing ligand （TRAIL） to induce the apoptosis of hepatoceilular carcinoma ceils and the mechanism involved. Methods Human hepatocellular carcinoma HepG2 ceils were cultured in vitro, The cytotuxic activity was determined using MTT assay. The apoptotic cell death was examined using the cell apoptosis ELISA detection kit and Flow cytometry with PI staining. The expression of Mcl-1 was analyzed using western blotting, Results Sorafenib enhanced TRAIL-induced apoptosis of hepatocellular carcinoma HepG2 cells, and inhibited the expression of Mcl-1 in a concentration and time dependent manner. The overexpression of Mcl-1 inhibited Sorafenib from enhancing apoptosis of hepatocellular carci- noma cells induced by TRAIL. Conclusion Sorafenib enhanced apoptosis of human hepatocellular carcinoma HepG2 cell line induced by TRAIL through downregulating the Mcl-1 expression.

关 键 词：肝癌 索拉菲尼 肿瘤坏死因子相关凋亡诱导配体 MCL-1 

分 类 号：R735.7[医药卫生—肿瘤]