抑制端粒酶活性引起肝癌细胞凋亡的caspase机制探讨  

The Molecular mechanisms are involved in the induction of apoptosis of human hepatocellular carcinoma cells HepG2 by inhibited telomerase activity

作　　者：郎伟宁[1] 邓志华[1] 

机构地区：[1]山西医科大学第二医院消化科,太原030001

出　　处：《中国医疗前沿》2011年第5期7-8,91,共3页China Healthcare Innovation

基　　金：国家自然基金(编号:30672405)

摘　　要：目的本文探讨hTERTp-TK/GCV系统诱导HepG2细胞凋亡的caspase分子机制。方法 hTERTp-TK/GCV转染HepG2,免疫印迹技术检测caspase-3,8,10,survivin活化裂解情况;MTT法检测caspase-8,3,10抑制剂对hTERTp-TK/GCV诱导HepG2细胞凋亡的抑制作用。结果免疫印迹技术结果显示随时间延长,caspase-8、3酶原逐渐减少、活化片断增多,caspase-10酶原无明显改变,survivin则逐渐减少;caspase-8抑制剂能明显抑制hTERTp-TK/GCV系统诱导的肝癌细胞凋亡,其抑制作用大于caspase-3抑制剂。结论 hTERTp-TK/GCV系统诱导的肝癌细胞凋亡主要是激活了细胞凋亡死亡受体途径上游的caspase-8引起的,同时还涉及caspase家族其它成员,caspase-10没有参与此凋亡过程,此外还涉及survivin的活性减少。Objective The aim of this study was to observe the molecular mechanisms are involved in the induction of apoptosis of HepG2 cells by hTERTp-TK/GCV system.Methods The changes of cleavage products of caspase-3,8,10,survivin were analyzed by western blot after the hTERTp-TK/GCV system treat ment of HepG2 cells.The inhibitors for Caspase-8,3,10 were used to block the apoptotic pathway of HepG2 cells by hTERTp-TK/GCV system through MTT.Results Western blotting showed that with time,caspase-8,3 zymogen decreased,the activation segment increased,while caspase-10 zymogen no significant change,but survivin is gradually reduced.Conclusions hTERTp-TK/GCV system induced apoptosis of HCC primarily activated death receptor pathway of apoptosis upstream of caspase-8 caused,also involves other members of the caspase family,such as caspase-3.Caspase-10 were not involved in the apoptotic process.In addition,involved in the activity of survivin reduced.

关 键 词：靶向基因治疗 肝癌 HTERT启动子 细胞凋亡 分子机制 

分 类 号：R735.7[医药卫生—肿瘤]