胆囊癌组织中Gab1蛋白表达及下调Gab1对胆囊癌细胞增殖、侵袭的影响

摘要

目的:探讨胆囊癌组织中Gab1蛋白表达及下调Gab1对胆囊癌细胞增殖、侵袭的影响.方法:选取2013年1月至2015年12月陕西省人民医院肝胆外科诊治的胆囊癌患者48例,免疫组化法检测胆囊癌、癌旁组织中Gab1蛋白表达;通过TargetScan数据库检索调控Gab1的microRNA;通过脂质体将miR-330-mimic转染GBC-SD细胞,利用细胞集落形成实验和裸鼠移植瘤模型研究miR-330下调Gab1蛋白表达对细胞增殖和侵袭能力的影响;通过Transwell小室研究miR-330下调Gab1蛋白对GBC-SD细胞侵袭能力的影响.结果:胆囊癌组织Gab1阳性表达率高于癌旁组织(P<0.000 1),miR-330可能具有下调Gab1表达的作用;miR-330-mimic转染GBC-SD细胞后,Gab1 mRNA表达减少(P<0.000 1),Gab1 蛋白表达减少(P<0.000 1);miR-330转染后,GBC-SD细胞克隆数目减少(P<0.000 1),Balb/c裸鼠肿瘤平均体积减小(P=0.000 3),移至Transwell下室的细胞数减少(P=0.000 2).结论:miR-330通过下调Gab1在体内、外抑制GBC-SD细胞的增殖和侵袭,miR-330、Gab1可作为胆囊癌诊疗工作中新的研究方向.%Objective:To investigate the expression of Gab1 in gallbladder carcinoma and the effect on GBC-SD cell proliferation and invasion after down-regulation of Gab1.Methods:The expression of Gab1 was determined in 48 patients with gallbladder carcinoma by immunohistochemistry.The probable microRNAs were predicted by TargetScan.The expression of Gab1 was determined after GBC-SD cells were transfected with miR-330,and the cell proliferation and invasion of GBC-SD cells were tested by cell colony formation,nude mice model and Transwell assay.Results:The positive rate of Gab1 was significantly higher in gallbladder carcinoma than that in para-cancer tissues (P<0.000 1).After miR-330 was transfected to GBC-SD cells,the expression of Gab1 was decreased,and the proliferation and invasion of gallbladder cancer cell were inhibited in vivo and vitro.Conclusion:miR-330 inhibits proliferation and invasion of gallbladder carcinoma cell by down-regulation of Gab1 in vivo and vitro.miR-330 and Gab1 may play an important role in gallbladder carcinoma.