DLC-1过表达抑制结肠癌细胞生长及与Wnt/β-catenin信号通路的关系  

Relationship between tumor suppressor gene DLC-1 and Wnt/ and β-catenin signal pathway

作　　者：王春毅[1] 王佳林[1] 刘洪[1] 傅仲学[1] 

机构地区：[1]重庆医科大学附属第一医院胃肠外科,重庆400016

出　　处：《重庆医科大学学报》2014年第12期1736-1739,共4页Journal of Chongqing Medical University

基　　金：重庆市卫生局医学科学技术研究资助项目(编号:2010-2-048)

摘　　要：目的:探讨在结肠癌细胞中抑癌基因DLC-1的作用及其与Wnt/β-catenin信号通路的关系。方法:以结肠癌SW480细胞系为实验对象,分为实验组(pc DNA3.1(+)-DLC-1组),阴性对照组[pc DNA3.1(+)组]及空白对照组(SW480组)。用携带抑癌基因DLC-1的重组慢病毒表达载体转染各组,用MTT法检测各组细胞增殖活性,用流式细胞仪检测各组凋亡率,用real-time PCR及Western blot分别检测各组Wnt/β-catenin信号通路相关基因β-catenin、GSK-3β和c-myc的表达水平。结果:慢病毒介导DLC-1过表达使结肠癌细胞SW480的增殖受到抑制,增殖率为0.546,凋亡率明显增加,为42.422+3.413。转染DLC-1基因的结肠癌SW480细胞中β-catenin和c-myc的m RNA及蛋白表达水平较空白对照组及阴性对照组均明显下降,而GSK-3β的m RNA及蛋白表达水平较空白对照组及阴性对照组则明显上升,差异具有统计学意义(P均=0.000)。结论:慢病毒介导DLC-1过表达在结肠癌中有明显的抑癌作用,这种作用与Wnt/β-catenin信号通路密切相关。DLC-1可能是Wnt/β-catenin信号通路的上游调节因子。Objective：To investigate the effect of tumor suppressor gene DLC-1 on Wnt/β-catenin signaling pathway in colon cancer cell line SW480. Methods：Human colon cancer cell line SW480 was taken as research object and was divied into 3 groups：pcDNA3.1 （＋）-DLC-1 group,pcDNA3.1 （＋） group and SW480 group. Each group was transfected with recombinant lentiviral vector containing DLC-1 gene. MTY was applied to detect cell proliferation and flow cytometry was performed to detect cell apoptosis. Real-time PCR and Western blot were preformed to detect the mRNA and protein expressions of Wnt/β-catenint signaling pathway related genes （β- catenin, GSK-3βand c-my）. Results：The proliferation of SW480 cells was significantly inhibited （the proliferation rate was 0.546） and the apoptosis was increased（the apoptosis rate was 42.422＋3.415） in pcDNA3.1 （＋）-DLC-1 group. Real-time PCR and Western blot determined that the mRNA and protein expressions of ^-catenin and c-myc were down-regulated, and the mRNA and protein expressions of GSK-313 were up-regulated（P=0.000）. Conclusion：DLC-1 plays a suppression role in colon cancer cell, which asso- ciates with Wnt/β-catenint signaling pathway. DLC-1 may be the upstream adjustment factor of Wnt/β-catenint signal pathway.

关 键 词：DLC-1 抑癌基因 结肠癌 WNT/Β-CATENIN信号通路 

分 类 号：R735.3[医药卫生—肿瘤]