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

The expression of Gab1 in gallbladder carcinoma and the effect on cell proliferation and invasion after down-regulation of Gab1

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Target Scan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 Gabl in gallbladder carcinoma and the effect on GBC - SD cell proliferation and invasion after down - regulation of Gabl. Methods： The expression of Gabl was determined in 48 patients with gallbladder carcinoma by immunohistochemistry. The probable microRNAs were predicted by Tar- getScan. The expression of Gabl 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 as-say. Results ： The positive rate of Gabl was significantly higher in gallbladder carcinoma than that in para - cancer tis-sues （P 〈0. 000 1） . After miR -330 was transfected to GBC - SD cells,the expression of Gabl was decreased,and the proliferation and invasion of gallbladder cancer cell were inhibited in vivo and vitro. Conclusion ： miR - 330 in-hibits proliferation and invasion of gallbladder carcinoma cell by down - regulation of Gabl in vivo and vitro. miR - 330 and Gabl may play an important role in gallbladder carcinoma.