幽门螺杆菌对CCAAT增强子结合蛋白α和Cx43表达的影响及其在胃癌发生中的作用

Effect of H.pylori on the expression of CCAAT enhancer binding protein a and Cx43 and its role in gastric carcinogenesis

目的:探讨CCAAT增强子结合蛋白α(CCAAT enhancer binding proteinα,C/EBPα)和间隙连接蛋白43(connexin43,Cx43)表达改变在H.pylori致胃癌中的作用。方法:扩大培养不同胃黏膜上皮细胞株(GES-1细胞、AGS细胞、SGC-7901细胞);胃镜下采集H.pylori感染慢性非萎缩性胃炎患者6例、胃癌前病变和胃癌患者各12例胃黏膜组织;采用realtime PCR法检测上述细胞和组织中C/EBPα和Cx43 mRNA的表达;同时将东亚型Cag A+H.pylori与GES-1细胞共培养24和48 h为实验组,以不加H.pylori的GES-1细胞株为对照组,培养24和48 h;采用real-time PCR法和Western印迹检测C/EBPα和Cx43 m RNA和蛋白的表达。结果:C/EBPα和Cx43 m RNA在AGS细胞、SGC-7901细胞中的表达均显著低于GES-1细胞(均P<0.05),且两者在SGC-7901细胞中的表达量较AGS细胞更低(均P<0.05);C/EBPα和Cx43 m RNA在胃癌胃黏膜组织中的表达明显低于慢性非萎缩性胃炎(均P<0.05)和胃癌前病变(均P<0.05),C/EBPα与Cx43表达呈正相关(胃癌前病变:r=0.679;胃癌:r=0.792,均P<0.05);实验组24,48 h的C/EBPα和CX43表达量在转录及蛋白水平均低于对照组(均P<0.05),且48 h表达量均低于24 h(均P<0.05)。结论:H.pylori感染可下调胃黏膜上皮细胞C/EBPα和CX43的表达,这可能与胃癌发生有关。

Objective： To explore the effect ofH. pylori on the expression of CCAAT enhancer binding proteina （C/EBPa） and connexin 43 （Cx43） in gastric carcinogenesis. Methods： Different gastric mucosal epithelial cell lines （GES-1 cells, AGS cells and SGC-7901 cells） were cultured. A total of 6 cases of chronic non-atrophic gastritis tissues, 12 cases of gastric precancerous lesions tissues and 12 cases of gastric cancer tissues were collected under endoscopy. The expression of C/EBPa and Cx43 mRNA in the above-mentioned cells and tissues was detected by real-time PCR. The GES-1 cells and East Asian CagA＋ H. pylori strains were co-cultured for 24 and 48 h as an experimental group, and those cell lines without H. pylori infection were cultured for 24 and 48 h as a control group. Real-time PCR and Western bolt were used to detect the expression ofmRNA and proteins of C/EBPa and Cx43 in GES-1 cells, respectively. Results= The expressions of C/EBPa and Cx43 mRNA in the AGS and SGC-7901 cells were lower than those in GES-1 cells （all P〈0.05）, and both of them decreased more profoundly in the SGC- 7901 cells than those in the AGS cells （both P〈0.05）. The expressions of C/EBPa and Cx43 mRNA were lower in the gastric cancer tissues than those in the chronic non-atrophic gastritis tissues （both P〈0.05） and gastric precancerous lesion tissues （both P〈0.05）. The C/EBPa expression was positively correlated with Cx43 expression （gastric precancerous lesion tissues： r=0.679, gastric cancer tissues： r=0.792; both P〈0.05）. Compared with the control group, the expressions of C/ EBPa and Cx43 mRNA and protein in the experimental group were decreased at 24 and 48 h after culture （both P〈0.05）, which were lower at 48 h than those at 24 h （both P〈0.05）. Conclusion： H. pylori infection can down-regulate the expressions of C/EBPa and Cx43 on gastric epithelial cells, which may be associated with gastric carcinogenesis.