胃泌素调节胆管癌细胞凋亡的初步研究

Effects of gastrin on apoptotic pathways in human cholangiocarcinoma cell line QBC939

目的探讨胃泌素 (gastrin)对胆管癌细胞凋亡的调节及机理。方法用TUNEL技术和定量RT PCR分别检测胃泌素 17(G 17)对QBC939人胆管癌细胞系白僵菌素诱发性凋亡指数 (AI)和bcl 2 /baxmRNA表达的影响 ,用反义寡核苷酸技术研究bcl 2基因在胃泌素调节细胞凋亡中的作用。结果与对照组比较 ,G 17组AI降低、bcl 2mRNA表达增强 (P <0 0 1) ,baxmRNA无变化 ;胃泌素受体拮抗剂L36 5 ,2 6 0 (L6 0 )可拮抗G 17对AI和bcl 2mRNA表达的影响 (P <0 0 1) ;反义bcl 2寡核苷酸转染可逆转G 17对AI的抑制 (P <0 0 1) ,正义和随机片段无作用。结论胃泌素能提高凋亡阈值、抑制胆管癌细胞凋亡 ,其机理与上调bcl

ObjectiveTo explore the effects of gastrin on the bcl-2-associated apoptotic pathways in cholangiocarcinoma.MethodsTUNEL technique and quantitative RT-PCR were used to examine the effects of gastrin-17(G-17) on the beauvericin-induced apoptotic index (AI) and expressions of bcl-2 and bax mRNAs. Antisense oligodeoxynucleotide (ODN) technology was conducted to investigate the role of bcl-2 in the gastrin-mediated inhibition of apoptosis in human cholangiocarcinoma cell line QBC939. ResultsThe AI and bcl-2 mRNA expression significantly decreased and increased respectively in the cells exposed to gastrin-17 compared with those of control cells (P<0 01), no change of bax mRNA was observed. These two actions of gastrin could be blocked by the gastrin receptor antagonist L365,260 (L60). Finally, the inhibitory effect of gastrin on apoptosis could also be abolished by bcl-2 antisense ODN, the sense and scrambled ODNs were ineffective. ConclusionsGastrin is able to increase the threshold for apoptosis by upregulating bcl-2 gene expression in human cholangiocarcinoma cells.