Endophilin A2与胃癌BGC-823细胞转移及上皮-间质转化的关系

Relationship between Endophilin A2 and metastasis of BGC-823/epithelial-mesenchymal transition in gastric cancer

目的:探究Endophilin A2在胃癌转移及上皮–间质转化(epithelial-mesenchymal transition,EMT)过程中的作用及相关机制。方法:通过免疫组织化学法测定37例胃癌原发灶组织和35例胃癌转移淋巴结中Endophilin A2蛋白的分布和表达情况。在BGC-823细胞转染腺病毒过表达Endophilin A2后,通过划痕实验和Trans well实验观察其迁移能力;Western印迹检测EMT及相关信号通路蛋白的水平。结果:免疫组织化学结果显示胃癌淋巴结转移灶中Endophilin A2蛋白的表达明显低于原发灶。BGC-823细胞中过表达Endophilin A2之后细胞的迁移能力降低,上皮细胞标志物上皮黏附蛋白(epithelium cadherin,E-cadherin)的表达升高,同时黏附蛋白辅助因子β-catenin的表达升高,而间质细胞标志物神经钙黏蛋白(nervous cadherin,N-cadherin)和波形蛋白vimentin的表达明显下降。Endophilin A2过表达之后,Notch和snail的表达也明显降低。结论:Endophilin A2与胃癌淋巴转移密切相关,过表达Endophilin A2可能通过Notch/snail通路抑制胃癌细胞BGC-823的EMT进程。

Objective： To investigate the effect of Endophilin A2 on the metastasis and epithelial-mesenchymal transition（EMT） in human gastric cancer and its underlying mechanism. Methods： The distribution and expression of Endophilin A2 in 37 cases of gastric cancer tissues and 35 cases of lymph node tissues with gastric cancer metastasis were detected by immunohistochemical SP method. Adenovirus expression vector were transfected into gastric cancer cell BGC-823 for over-expression of exogenous Endophilin A2. Scratch test and transwell assay were used to detected tumor cell migration. The protein expressions of E-cadherin, β-catenin, N-cadherin, vimentin, Notch and snail were determined by Western blot. Results： The results of immunohistochemistry showed that the levels of Endophilin A2 protein expression were lower in the gastric cancer tissues of metastasis than that in the primarily site. Over-expression of Endophilin A2 levels were accompanied with higher expressions of E-cadherin, β-catenin, while decreased the expression of N-cadherin, vimentin, Notch and snail in BGC-823 cells. Conclusion： Endophilin A2 is highly related to the metastasis of gastric cancer. Over-expression of Endophilin A2 may suppresses the EMT progress via Notch/snail pathway in BGC-823 cells.