Survivin对人胆管癌细胞凋亡相关信号通路的作用机制  

Investigation of mechanisms underlying inhibition of apoptosis-related signaling inhibited by survivin in human cholangiocarcinoma cells

作　　者：卢昕[1] 肖新波[1] 

机构地区：[1]武汉市第一医院胃肠外科,湖北省武汉市430022

出　　处：《世界华人消化杂志》2012年第8期644-648,共5页World Chinese Journal of Digestology

基　　金：武汉市卫生局基金资助项目;No.0270819~~

摘　　要：目的:探讨Survivin基因对人胆管癌细胞凋亡信号通路的调节机制.方法:构建针对Survivin基因的siRNA和对照siRNA,分别转染QBC939人胆管癌细胞,Western blot检测siRNA对细胞Survivin的干扰效果.继而分别用流式细胞仪,激酶活性测定和Westernblot检测不同Survivin表达状态下,QBC939细胞的凋亡状态,caspase-3的活性和caspase-3,caspase-9及procaspase-9凋亡信号分子的表达.结果:siRNA-Survivin显著抑制Survivin在QBC939细胞的表达(P<0.05).Survivin表达抑制后,QBC939细胞凋亡明显增加(18.9%±2.3%,P<0.05),caspase-3活性显著升高(0.83±0.15,P<0.01),caspase-3和caspase-9表达明显上调(P<0.05),而procaspase-9表达降低(P<0.05).未转染和转染对照siRNA的QBC939细胞上述变化无显著性差异(P>0.05).结论:Survivin基因通过促进procaspase-9的活化以阻止caspase-3和caspase-9的激活从而抑制胆管癌细胞的凋亡.AIM： To explore the mechanisms by which survivin regulates apoptosis-related signaling in human cholangiocarcinoma cells. METHODS： SiRNA targeting the survivin gene and control siRNA were constructed and transfected into human cholangiocarcinoma cell line QBC939. The knockdown of survivin expression in QBC939 cells was confirmed by Western blot. Apoptosis rate was evaluated by flow cytometry. Capase-3 activity was determined using a commercial kit, and expression of caspase-3, caspase-9 and procaspase-9 in QBC939 cells was detected by Western blot. RESULTS： Transfection of siRNA targeting the survivin gene significantly inhibited survivin expression in QBC939 cells （P 0.05）. Inhibition of survivin significantly increased apoptosis rate （18.9% ± 2.3%, P 0.05） and caspase-3 activity （0.83 ± 0.15, P 0.01）, up-regulated the expression of caspase-3 and caspase-9 （both P 0.05）, and down-regulated the expression of procaspase-9 （P 0.05） in QBC939 cells. No significant differences were observed in the above parameters between non-transfected QBC939 cells and cells transfected with control siRNA （all P 0.05）. CONCLUSION： Survivin inhibits apoptosis of cholangiocarcinoma cells possibly by inhibiting caspase-3 and caspase-9 activities through activating procaspase-9.

关 键 词：SURVIVIN基因 凋亡 胆管癌细胞 

分 类 号：R735.8[医药卫生—肿瘤]