外源性胃泌素对胃癌细胞凋亡和凋亡调控基因bcl-2的影响

背景与目的:大量研究表明,外源性胃泌素对胃癌、结肠癌等胃肠道肿瘤细胞有促生长作用,但胃泌素是否参与了细胞的凋亡调控尚未见报道。本文旨在探讨胃泌素在胃癌细胞凋亡调控中的作用。方法:应用流式细胞仪观察胃泌素及其受体拮抗剂丙谷胺对MKN45胃癌细胞凋亡的影响;ABC免疫组化法测定细胞bcl-2基因的表达。结果:细胞培养48h后,胃泌素组细胞凋亡百分率为(1.39±0.54)%,明显低于对照组的(8.58±0.67)%(P<0.01);胃泌素组bcl-2基因阳性率为(22.3±5.3)%,明显高于对照组的(12.2±1.8)%(P<0.01),且随着时间延长表达率进一步增加。联合应用丙谷胺后上述作用消失。结论:胃泌素可能通过诱导细胞bcl-2基因的表达而抑制细胞的凋亡,丙谷胺可阻断胃泌素的凋亡调控作用。

Effect of external gastrin on apoptosis and expression of bcl-2 gene in gastric cancer cells

BACKGROUND & OBJECTIVE: It has been reported that external gastrin could facilitate the growth of the cells of gastrointestinal carcinomas. However, the modifying effect of gastrin on apoptosis of the gastric carcinoma has not been well appreciated. This study was designed to investigate the modifying effect of gastrin on apoptosis of the stomach cancer cell. METHODS: Flow cytometric analysis (FCM) and immunohistochemical dyeing are used to measure the rates of apoptosis and expression of bcl-2 gene in MKN45 cell line treated with gastrin and its receptor antagonist. RESULTS: Forty-eight hours later, the percentage of apoptosis cell in gastrin group was 1.39 +/- 0.54%, lower than that in control group (8.58 +/- 0.67%) (P < 0.01), but the expression rate of bcl-2 in gastrin treatment group was 22.3 +/- 5.3% higher than that in control group (P < 0.01). These effects were vanished after combined treatment with proglumide. CONCLUSIONS: External gastrin may restrain the apoptosis of MKN45 cell by inducing the expression of bcl-2 gene, and proglumide can block these effects of gastrin.