Gastrin/CCK与胆管癌细胞bcl-2/bax蛋白表达的关系

目的 初步探讨Gastrin/CCK对胆管癌细胞bcl-2/bax蛋白表达的调节作用。方法 原位杂交和免疫组化分别检测Gastrin/CCK受体mRNA和bcl-2/bax蛋白在40例胆管癌组织标本中的表达、分析两者间关系,流式细胞术研究Gastrin/CCK及其受体拮抗剂对QBC939人胆管癌细胞系bcl-2/bax蛋白表达的影响。结果Gastrin/CCK受体 mRNA和bcl-2/bax蛋白在胆管癌组织和细胞系中均有表达;Gastrin/CCK-B受体阳性胆管癌标本bcl-2表达率高于其阴性者（P<0.01）;Gastrin-17或CCK-8S（10~（-8）mol·L~（-1）×48h）能刺激QBC939细胞bcl-2表达、同时加入L365,260或 L364,718（10~（-8）mol·L~（-1））可逆转,CCK-SS还能抑制bax表达、L364,718可逆转（P<0.01或P<0.05）。结论Gastrin/CCK可通过其受体后途径上调胆管癌细胞bcl-2表达,“CCK→CCK-A受体”信号还可能具有抑制bax表达的作用。

Relation of bcl- 2 and bax protein expressions to gastrin and CCK and their receptors in cholangiocarcinoma

Objective To explore the regulative effects of gastrin and CCK on bcl - 2 and bax protein expressions in cholangiocarcinoma. Methods Hybridization in situ and immunohistochemistry were conducted to detect the expressions of gastrin/CCK receptor mRNAs and bcl - 2/bax proteins in 40 cases of cholangiocarcinoma tissues, and flow cytometry was applied to study the effects of gastrin/CCK and their receptor antagonists on bcl - 2/bax protein expressions in human cholangiocarcinoma cell line QBC939. Results The CCK - A and gastrin/CCK - B receptors were both expressed in cholangiocarcinoma tissue and established cell line, as well as bcl - 2 and bax proteins. In cholangiocarcinoma tissues, the expression ratio of bcl - 2 in gastrin/CCK - B receptor positive cases was significantly higher than that in negative cases ( P <0.01). In serum free medium, gastrin - 17 or CCK- 8S( 10- 8mol'L-1 x 48 h) significantly stimulated bcl - 2 expression in QBC939 cells, and this action could be blocked by L365, 260 and 1364, 718 (10-8mol-L-1); CCK-8S also showed the ability to inhibit the bax expression in QBC939 cells, which could be abolished by 1364, 718 ( P < 0.01 or P < 0.05). Conclusions Gastrin and CCK are able to upregulate bcl - 2 gene expression via their classical receptors, CCK might also have the ability to inhibit bax expression via CCK - A receptor in chanlan-giocinoma cell.