幽门螺杆菌通过诱导上调B细胞特异性Moloney小鼠白血病病毒整合位点1(Bmi-1)表达促进人胃癌细胞的侵袭

Helicobacter pylori promotes gastric cancer metastasissvia up-regulating the expression of Bmi-1

目的验证幽门螺杆菌(H.pylori)能够通过诱导B细胞特异性Moloney小鼠白血病病毒整合位点1(Bmi-1)高表达促进胃癌细胞的转移。方法收集82名胃癌患者手术标本,实时定量PCR和免疫组织化学染色检测胃腺癌组织Bmi-1的表达,并回顾性分析Bmi-1表达与胃癌病理特征及预后的相关性;采用pLPCX-Bmi-1质粒转染和H.pylori感染GES-1细胞,在过表达Bmi-1后,TranswellTM实验检测细胞的侵袭能力、流式细胞术检测细胞周期和细胞凋亡。结果胃癌组织中Bmi-1的mRNA及蛋白表达均高于癌旁组织,且高表达Bmi-1与肿瘤浸润程度、TNM分期、分化程度、淋巴结转移及H.pylori感染相关;转染及H.pylori感染所致的Bmi-1表达上调后,GES-1细胞具有更高的侵袭能力和较低的凋亡比率。结论H.pylori感染能上调Bmi-1表达,抑制胃癌细胞的凋亡并促进其侵袭。

Objective To clarify whether Helicobacter pylori(H.pylori)can promote metastasis of gastric cancer cells via the high-expression of induced B cell specific Moloney murine leukemia virus integration site 1(Bmi-1).Methods The gastric cancer tissue specimens from 82 patients were collected for this study.The protein and gene expression level of Bmi-1 in gastric adenocarcinoma tissue were detected by immunohistochemistry and real time quantitative PCR,respectively.And meanwhile the correlation between Bmi-1 levels and pathological features,and prognosis of gastric cancer were analyzed retrospectively.Then,the GES-1 cells were transfected with pLPCX-Bmi-1 plasmid and infected with H.pylori respectively.After the Bmi-1 overexpression in GES-1 cells,the invasion ability of the GES-1 cells was detected by Transwell assay,and the cell cycle and apoptosis were detected by flow cytometry.Results The mRNA and protein of Bmi-1 expression in gastric cancer tissues were higher than tumor-adjacent tissue,and the high expression of Bmi-1 was positively correlated with tumor invasion,TNM stage,tumor differentiation,lymph node metastasis and H.pylori infection.When expression of Bmi-1 was up-regulated as a result of H.pylori infection or pLPCX-Bmi-1 transfection,the GES-1 cells had higher invasiveness and lower apoptosis rate with the above treatment respectively.Conclusion H.pylori infection can inhibit the apoptosis of gastric cancer cells and promote their invasion via up-regulating expression of Bmi-1.