幽门螺杆菌对AGS细胞DNA错配修复基因表达的影响

Effects of Helicobacter pylori on expression of DNA mismatch repair genes in AGS cell line

目的体外观察幽门螺杆菌对 AGS 细胞 DNA 错配修复(mismatch repair,MMR)基因蛋白和 mRNA 表达的影响,以确定不同疾病来源幽门螺杆菌对 MMR 基因表达的影响是否存在差异。方法 AGS 细胞分别与5株分离自胃癌和5株分离自胃炎患者的幽门螺杆菌共培养。逆转录-聚合酶链反应(RT-PCR)和 Western 印迹法检测 hMSH2和 hMLH1基因 mRNA 和蛋白表达,同时以肠道致病性大肠杆菌作为细菌对照。结果胃炎菌株和大肠杆菌基本不影响 hMLH1和 hMSH2基因 mRNA 和蛋白表达,而所有胃癌菌株都能下调 hMLH1和 hMSH2基因 mRNA 和蛋白表达。结论胃癌菌株与胃炎菌株对胃癌细胞 MMR 的影响存在差异,提示部分幽门螺杆菌菌株可能通过损害细胞 MMR 功能促进胃黏膜上皮细胞内 DNA 突变累积,增加幽门螺杆菌长期感染时胃癌发生的危险性。

Objective To investigate the effects of Helicobacter pylori （H. pylori） strains from the patient with gastric cancer on the expression of DNA mismatch repair （MMR） genes in AGS cells in vitro. Methods AGS cells were co-cultured with ten strains of H. pylori from five patients with gastric cancer and five patients with gastritis respectively. The expressions of DNA MMR genes （hMSH2 and hMLH1 ） in mRNA and protein levels were determined by RT-PCR and Western blot. The enteropathogenic E. coli served as a bacterial control. Results E. coli and H. pylori strains from gastritis have no effects on the expression of hMSH2 and hMLH1 in both protein and mRNA levels on the whole, while all the H. pylori strains from gastric cancer reduced expression levels of hMSH2 and hMLH1. Conclusions There are different effects between H. pylori strains from gastric cancer and those from gastritis on DNA MMR in AGS cell line, indicating that infection of some H. pylori strains might lead to the inhibition of DNA MMR, and that in turns increases the risk of gastric carcinogenesis during chronic H. pylori infection.