Sulindac通过抑制Wnt通路诱导SMMC-7721肝癌细胞凋亡  

Sulindac induces SMMC-7721 cells apoptosis through inhibiting Wnt pathway

作　　者：冯晓铖[1] 王晓明[1] 张毅[1] 李姣[1] 申宗侯[1] 

机构地区：[1]复旦大学上海医学院生物化学与分子生物学系,上海200032

出　　处：《复旦学报（医学版）》2007年第4期522-526,共5页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金项目(30370343)

摘　　要：目的初步研究Wnt通路及蛋白激酶B(PKB)在非甾体类抗炎药sulindac诱导人肝癌SMMC-7721细胞凋亡过程的作用。方法利用流式细胞仪检测肝癌细胞7721的凋亡,利用Western blot检测caspase-9、PARP(poly ADP-ribose polymerase)等凋亡相关分子的剪切,β连环蛋白(β-catenin)及糖原合酶激酶3β(GSK3β)与蛋白激酶B(PKB)磷酸化水平的变化,利用RT-PCR检测β-catenin及c-myc的mRNA水平。结果sulindac能够诱导SMMC-7721细胞凋亡,显著降低β-catenin的蛋白水平,抑制GSK3β9位丝氨酸的磷酸化,同时促使caspase-9、PARP等凋亡相关分子发生剪切;β-catenin的mRNA水平未见变化;PKB的磷酸化水平未见降低,反而略有增高。结论sulindac能够通过抑制Wnt通路,促进β-catenin的蛋白降解,降低其蛋白水平,诱导SMMC-7721细胞凋亡,且该作用不依赖PKB活性的抑制。Purpose To study the role of Wnt pathway and protein kinase B （PKB） in sulindac,one of nonsteroidal anti-inflammatory drugs,induced human hepatocellular carcinoma SMMC-7721 cell apoptosis. Methods The apoptosis of hepatocellular carcinoma SMMC-7721 cells were detected by flow cytometry. Caspase-9, PARP（poly ADP-ribose polymerase）, β-catenin, GSK3β and protein kinase B（PKB） were detected by Western blot. The mRNA level of β-catenin and c-myc were detected by PTPCR. Results Sulindac could cause SMMC-7721 cells death through cleavage of caspase-9 and PARP, and decline the protein level of β-catenin but not the mRNA level. Also the phosphorylation level of GSK3β was inhibited. However,the phosphorylation level of PKB did not decline but slightly enhanced. Conclusions by declining the protein Sulindac induced SMMC-7721 cells apoptosis through inhibiting Wnt pathway level of β-catenin,which was independent of PKB inhibition.

关 键 词：凋亡 WNT通路 Β-连环蛋白 人肝癌细胞 

分 类 号：R735.7[医药卫生—肿瘤]