TRAIL的诱导肿瘤细胞凋亡与临床  

Progress and clinical application of TRAIL-induced apoptosis in cancer

作　　者：范清林[1] 宋礼华[2] 魏伟[1] 

机构地区：[1]安徽医科大学临床药理研究所,合肥230032 [2]安徽省生物研究所,合肥230032

出　　处：《中国药理学通报》2003年第9期976-981,共6页Chinese Pharmacological Bulletin

基　　金：安徽省"十五"生物医药重大产业化专项课题 No 0 13 0 3 0 0 1;安徽省自然科学基金资助课题 No 0 10 43 3 0 2

摘　　要：TRAIL是最近发现的属肿瘤坏死因子家族新成员 ,它能选择性地杀伤多种肿瘤细胞而对正常细胞没有细胞毒性。它的作用机制主要通过细胞膜的表面死亡受体DR4和DR5介导细胞的凋亡信号 ,激活细胞内的多种诱导细胞凋亡蛋白的表达。主要的途径是通过TRAIL与死亡受体结合后促进DISC的形成和caspase8的激活 ,然后启动非依赖线粒体的凋亡途径和线粒体的凋亡途径。非线粒体凋亡途径通过激活的csapase8直接激活caspase3,从而启动细胞的凋亡。线粒体依赖途径通过激活的tBID导致细胞色素C的释放 ,与Apaf1和caspase9形成凋亡小体导致细胞的凋亡。通过以往的研究表明 ,非融合表达的TRAIL能明显诱导多种肿瘤细胞的凋亡 ,对正常人和猴的肝细胞没有细胞毒性 。TNF related apoptosis inducing ligand (TRAIL) is a new identified member of TNF family, which selectively kills a broad spectrum of tumor cells, but nontoxic to most normal cells. TRAIL triggers tumor cell apoptosis via death receptor DR4 and DR5 anchored in the cell surface, which is mediated through intracellular induced apoptosis proteins. The major pathway of its action proceeds through the formation of DSIC and activation of caspase8. The apoptotic processes follow two signal pathways, namely the mitochondrial independent activation of caspase3, and mitochondrial dependent apoptosis through the cleavage of BID by caspase8, the release of cytochrome C, the formation of apoptosome, and activation of caspase9 and the downstream apoptosis. In previous researches, it is shown that nontagged TRAIL proved to be noncytotoxic to hepatocytes in monkeys and chimpanzees and to human normal hepatocytes. Thus, the nontagged TRAIL has attracted great attention in recent years as a promising anti cancer reagent.

关 键 词：肿瘤坏死因子相关凋亡诱导配体 TRAIL 细胞 凋亡 死亡受体 胱冬酶 CASPASE 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学] R292.11[医药卫生—基础医学]