Gab1在胆管癌中的表达以及作用机制研究  

Expression and mechanism of Gab1 in cholangiocarcinoma

作　　者：夏云展[1] 解寒冰[1] 孙德利[1] 杨大勇[1] 

机构地区：[1]郑州人民医院普外科,河南郑州450003

出　　处：《中国现代医学杂志》2015年第19期31-35,共5页China Journal of Modern Medicine

摘　　要：目的探讨Gab1在胆管癌细胞中的表达以及其作用机制。方法正常胆管上皮细胞系HIBEC以及人胆管癌细胞系QBC939以及RBE作为研究对象,Western blot检测胆管癌细胞中Gab1的表达水平,Transwell和CCK8法检测Gab1对胆管癌细胞增殖和迁移的影响;并且用抑制剂PF2341066处理胆管癌细胞后,观察其对裸鼠移植瘤的影响。结果 Gab1在胆管癌细胞中发生明显的磷酸化;Gab1表达被干扰后,胆管癌细胞的增殖以及迁移能力受到明显的抑制;应用小分子抑制剂PF2341066对Gab1以及其下游信号磷酸化具有抑制作用;PF2341066明显抑制了胆管癌细胞的增殖以及迁移能力,并且PF2341066对胆管癌细胞增殖的抑制作用呈时间以及浓度依赖;应用抑制剂PF2341066后,裸鼠的肿瘤体积增长缓慢,肿瘤组织中Gab1的磷酸化水平明显降低,并且肿瘤组织中增殖标志物Ki67的阳性率明显下降。结论 Gab1在胆管癌细胞中明显活化,并且能够促进癌细胞的增殖和迁移,PF2341066可以有效的抑制Gab1的活化水平,缩小肿瘤体积。[ Objective ] To investigate the expression of Gabl in cholangiocarcinoma and its mechanism. [ Methods] Using normal biliary epithelial cell lines HIBEC, human cholangioeareinoma cell lines QBC939 and RBE as the research subjects, the expression of Gabl was detected by western blot; cell proliferation and migration were de- tected by transwell and CCK 8; the effects of Gabl and PF234166 were observed on nude mice. [Results] Gabl was activated in cholangiocarcinoma cells; the proliferation and migration was significantly inhibited after expression of Gabl was disturbed; Gabl and its downstream signaling were inhibited by PF2341066; PF2341066 significantly inhibited the proliferation and migration of cholangiocarcinoma cells, and the inhibition of eholangiocarcinoma cell proliferation by PF2341066 was in a time- and concentration-dependent manner; the tumor volume of nude mice significantly reduced, the phosphorylation levels of Gabl in tumor tissue were significantly reduced, and the expres- sion of tumor proliferation marker Ki67 was significantly decreased after applying inhibitors PF2341066. [ Conclusions] Gabl is activated in cholangiocarcinoma cells, and can promote the proliferation and migration of cancer cells, PF2341066 can effectively inhibit the activation level of Gabl and reduce the tumor volume.

关 键 词：Gab1 胆管癌 小分子抑制剂PF2341066 

分 类 号：R735.8[医药卫生—肿瘤]