Wnt／β-连环素信号通路对肝细胞癌信号分子的调节作用及其意义  

The role and significance of Wnt/ β-catenin signaling pathway regulating the signaling molecules in hepatocellular carcinoma

作　　者：王新红[1,3] 孙逊[2] 孟祥伟[1] 吕志武[3] 刘明娜[3] 裴风华[3] 

机构地区：[1]吉林大学第一医院胃肠内科,长春130012 [2]吉林大学第一医院理科,长春130012 [3]哈尔滨医科大学附属第二医院消化内科

出　　处：《中华肝脏病杂志》2010年第9期672-675,共4页Chinese Journal of Hepatology

摘　　要：目的 研究肝细胞癌中Wnt/β-连环素信号传导通路与糖原合成激酶（GSK）-3 β、STAT3、Smad3和人端粒酶逆转录酶（TERT）的关系及其意义.方法 用RNAi技术将针对β-连环素的siRNA转染入肝癌细胞系HepG2细胞中沉默β-连环素基因,于72h和96h提取蛋白质,用Western blot法检测β-连环素、GSK-3 β、p-GSK 3 β、STAT3、Smad3和TERT蛋白质的表达.用Student＇s t检验及方差分析进行统计学分析.结果 针对β-连环素的siRNA转染HepG2细胞72 h和96 h均可抑制β-连环素蛋白质的表达,且96 h比72 h的表达略有增加（t=4.43,P＜0.05）,而GSK-3 β及p-GSK-3 β的蛋白质表达于转染后72 h和96 h依次增加（tGSK 3β=4.98,tp-GSK-3β=29.83,P值均＜0.05）;STAT3的蛋白质表达于转染前后一致,差异无统计学意义（F=0.49,P＞0.05）;smad3的蛋白质表达于转染后72 h增加（t=10.67,P＜0.05）,96 h减少至原有水平（与转染前比较,t=0.90,P＞0.05）;TERT的蛋白质表达于转染后72 h减少（t=4.18,P＜0.05）,96 h增加至原有水平（t=1.26,P＞0.05）.结论 肝细胞癌中Wnt/β-连环素信号通路可能通过调节GSK-3 β、p-GSK-3 β、Smad3、TERT蛋白质的表达来参与肝癌的发生和发展过程;而与STAT3蛋白质的表达无关.Objective To investigate the role and significance ofWnt/β -catenin signaling pathway regulating GSK-3 β, STAT3, Smad3 and TERT in hepatocellular carcinoma （HCC）. Methods The HCC cell line HepG2 was transfected with small interfering RNA （siRNA） directed against β -catenin. Proteins were extracted and the expressions of β -catenin, GSK-3 β, p-GSK-3 β, STAT3, Smad3 and TERT were detected by Western blot at 72 h and 96 h respectively after transfection. Results β -catenin expression was inhibited at both time points and the expression at 96 h was higher than that at 72 h （t = 4.43, P 〈 0.05）. Interestingly, GSK-3 β and p-GSK-3 β expressions increased gradually at 72 and 96 h （tGSK-3 β = 4.98, tp-GSK-3 β = 29.83, P 〈 0.05）respectively, and STAT3 expression showed no alteration after transfection （F = 0.49, P 〉 0.05）. Smad3expression was increased at 72 h （t = 10.67, P 〈 0.05） and decreased to normal at 96 h （t = 1.26,P 〈 0.05）, while TERT expression decreased at 72 h （t = 4.18, P 〈 0.05） and increased to normal at 96 h （t = 1.26, P 〉 0.05）. Conclusions Wnt/ β -catenin signaling pathway is related to the expressions of GSK-3 β, Smad3 and TERT, but perhaps not related to STAT3 protein expression in HCC. It suggested that Wnt/ β -catenin signaling pathway might participate in HCC genesis and development through regulating the above three factors.

关 键 词：癌 肝细胞 RNA干扰 Β-连环素 信号传导通路 端粒酶 

分 类 号：R735.7[医药卫生—肿瘤]