熊去氧胆酸诱导 HepG2和 SMMC-7721肝癌细胞凋亡的机制  

Ursodeoxycholic acid induced apoptosis of human hepatoma cells HepG2 and SMMC-7721 by mitochondrial-mediated pathway

作　　者：吴端 周剑寅[2] 尹震宇[2] 刘平果[2] 赵一麟[2] 刘建明[2] 王效民[2] 

机构地区：[1]中国核工业北京401医院外科,102413 [2]厦门大学附属中山医院肝胆外科厦门市消化疾病诊治中心福建省慢性肝病肝癌重点实验室

出　　处：《中华医学杂志》2014年第44期3522-3526,共5页National Medical Journal of China

基　　金：国家重大传染病防治科技重大专项“十二五计划”（2012ZX10002-011-005）；国家自然科学基金（81171976）；福建省临床重点专科建设项目

摘　　要：目的：初步考察熊去氧胆酸（ UDCA）对肝癌细胞的增殖抑制和诱导凋亡的作用及机制。方法以人肝癌细胞HepG2、SMMC－7721为模型，熊去氧胆酸干预，利用MTT、倒置显微镜、荧光显微镜、流式细胞术、Western 印迹，分别观察和检测细胞增殖、细胞凋亡以及凋亡相关基因Bax、Bcl－2、Fas的表达情况。结果 UDCA显著抑制肝癌细胞生长，具有量效和时效关系， UDCA 400μg／ml作用HepG272h后细胞抑制率达到55．8％，作用48 h后HepG2、SMMC－7721两株细胞IC50分别为397．3、387．7μg／ml；UDCA诱导肝癌细胞凋亡，流式细胞仪检测结果显示，200μg／ml UDCA作用48 h后HepG2[对照组（1．37±0．61）％，UDCA 组（14．28±2．62）％]、SMMC－7721细胞[对照组（1．04±0．46）％，UDCA组（14．08±2．08）％]均表现出明显的早期凋亡，且差异具有统计学意义（P＜0．01），同时显著上调Bax和下调Bcl－2表达，P＜0．05。结论 UDCA抑制人肝癌细胞HepG2、SMMC－7721增殖，通过线粒体通路诱导肝癌细胞凋亡。Objective To explore the effects and underlying mechanisms of ursodeoxycholic acid on human hepatoma cells.Methods HepG2 and SMMC-7721 HCC cell lines were respectively treated with ursodeoxycholic acid .And cell proliferation , apoptosis and the expression of Bax/Bcl-2 gene were detected by methyl thiazolyl tetrazolium （ MTT ） , inverted microscopy , fluorescent microscopy , flow cytometry and Western blot.Results Ursodeoxycholic acid significantly inhibited the proliferation of human hepatoma cells in a concentration-and time-dependent manner.The half maximal inhibitory concentrations （IC50） of HepG2 and SMMC-7721 were 397.3 and 387.7μg/ml respectively after a 48-hour treatment of 400μg /ml ursodeoxycholic acid.And it also induced the apoptosis of HepG 2 and SMMC-7721 cells, up-regulated Bax gene and down-regulated Bcl-2 gene. Conclusion Ursodeoxycholic acid inhibits the proliferation of hepatoma cells and induce apoptosis by mitochondrial-mediated pathway .

关 键 词：熊去氧胆酸 癌 肝细胞 凋亡 

分 类 号：R735.7[医药卫生—肿瘤]