幽门螺杆菌诱导线粒体未折叠蛋白反应对胃癌细胞增殖的影响  

Effect of Helicobacter pylori induced mitochondrial unfolded protein response on gastric cancer cell proliferation

作　　者：陈吉丽 李雷蕾 陈源佳[1,2] 赵艳 谢渊 周建奖[1,2] Chen Jili;Li Leilei;Chen Yuanjia;Zhao Yan;Xie Yuan;Zhou Jianjiang(School of Basic Medical Sciences,Guizhou Medical University,Guiyang 550000;Key Laboratory of Molecular Biology,Guizhou Medical University,Guiyang 550000;Dept of Oncology,Affiliated Hospital of Guizhou Medical University,Guiyang 550000)

机构地区：[1]贵州医科大学基础医学院,贵阳550000 [2]贵州医科大学分子生物学重点实验室,贵阳550000 [3]贵州医科大学附属医院肿瘤科,贵阳550000

出　　处：《安徽医科大学学报》2025年第2期300-306,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:32160166、82260405);贵州省科技计划项目(编号:黔科合支撑[2020]4Y026号)。

摘　　要：目的从线粒体未折叠蛋白反应(UPR MT)角度研究幽门螺杆菌(Hp)诱导胃癌细胞增殖的机制。方法用Hp感染C57BL6/J小鼠、人胃癌细胞AGS和SGC-7901,提取细胞线粒体蛋白,Western blot检测UPR MT的相关指标:激活转录因子5(ATF5),热休克蛋白60(mtHSP60)、热休克蛋白70(mtHSP70)及线粒体蛋白酶(ClpP)的表达。用免疫组织化学定位4个蛋白质在小鼠胃组织中的表达部位。用Hp感染AGS和SGC-7901细胞,RTCA和CCK-8检测细胞增殖。最后,利用UALCAN数据库中TCGA样本分析4个指标在胃癌组织中的表达。结果Hp感染能显著促进C57BL6/J小鼠胃上皮细胞、人胃癌细胞AGS和SGC-7901线粒体中ATF5、mtHSP60、mtHSP70、ClpP的表达,促进胃癌细胞增殖。与TCGA样本中人正常胃组织比较,ATF5、mtHSP60、mtHSP70、ClpP在胃癌组织中高表达,差异均有统计学意义(均P<0.01)。结论Hp感染能够诱导胃上皮细胞及胃癌细胞发生UPR MT,促进细胞增殖。Objective To explore the mechanism of proliferation of gastric cancer cells induced by Helicobacter pylori(Hp)from the perspective of the mitochondrial unfolded protein response(UPR MT).Methods C57BL6/J mice,human gastric cancer cells AGS and SGC-7901 cells were infected with Hp,mitochondrial proteins were extracted,and the expressions of UPR MT,including activation of transcription factor 5(ATF5),heat shock protein 60(mtHSP60),heat shock protein 70(mtHSP70)and mitochondrial protease(ClpP),were detected by Western blot.Immunohistochemistry was used to locate the expression sites of 4 proteins in mouse gastric tissue.AGS and SGC-7901 cells were infected with Hp,and cell proliferation was detected by RTCA and CCK-8.Finally,the expression of four indexes in gastric cancer tissues was analyzed by TCGA samples in the UALCAN database.Results Hp infection could significantly promote the expression of ATF5,mtHSP60,mtHSP70 and ClpP in the mitochondria of gastric epithelial cells of C57BL6/J mice,AGS and SGC-7901 cells,and promote the proliferation of gastric cancer cells.When compared to normal gastric tissues in TCGA samples,ATF5,mtHSP60,mtHSP70,and ClpP were highly expressed in gastric cancer tissues,with statistically significant difference(all P<0.01).Conclusion Hp infection can induce UPR MT in gastric epithelial cells and gastric cancer cells,which in turn promotes cell proliferation.

关 键 词：幽门螺杆菌 胃癌细胞 线粒体未折叠蛋白反应 细胞增殖 线粒体蛋白 激活转录因子5 

分 类 号：R378[医药卫生—病原生物学]