线粒体途径在幽门螺杆菌诱导胃癌细胞凋亡中的作用

Role of mitochondrial pathway in apoptosis of gastric cancer cell line SGC-7901 induced by Helicobacter pylori

目的探讨线粒体途径在幽门螺杆菌(H.pylori)诱导胃癌细胞凋亡中的作用。方法采用流式细胞术检测H.pyloriNCTC 11637诱导的SGC-7901细胞凋亡,RT-PCR和Western blot法检测H.pylori感染对线粒体途径相关基因和蛋白表达的影响,并观察Caspase抑制剂对H.pylori所致SGC-7901细胞凋亡的影响。结果H.pylori能够在体外直接诱导SGC-7901细胞凋亡,6、12、24 h和48 h的凋亡率分别为6.30%、11.57%、8.63%和7.22%;H.pylori能够呈时间依赖性地上调SGC-7901细胞的Bax蛋白表达,并促进Caspase-9和3的激活;Caspase-9和3抑制剂能够显著抑制NCTC 11637所致的SGC-7901凋亡,而Caspase-8抑制剂仅能部分抑制约20%NCTC 11637所致的SGC-7901凋亡。结论H.pylori可引起SGC-7901细胞Bax基因和蛋白表达升高,激活Caspase-9和Caspase-3,且主要通过线粒体途径诱导细胞凋亡。

Objective To evaluate the role of mitochondrial pathway in apoptosis of gastric cancer cell line SGC-7901 induced by ttelicobacter pylori（ H. pylori）. Methods Apoptosis was evaluated in 5GC-7901 cells by flow cytometry. RT-PCR and Western blotting were used to measure the expressions of genes and proteins as- sociated with mitochondrial pathway. Effect of caspase inhibitors on apoptosis induced by H. pylori strain NCTC11637 was investigated. Results NCTC11637 directly induced apoptosis in 5GC-7901 cells. Apoptotic rate was 6.30% , 11.57% , 8.63% and 7.22% respectively at 6, 12, 24 and 48 h after cocuhure with H. py- lori. H. pylori upregulated the expression of Bax, and induced a time-dependent activation of caspase-9 and -3. Apoptosis was inhibited significantly by pre-incubation with the inhibitors of caspase-9 and -3. Caspase-8 inhib- itor reduced H. pylori-induced apoptosis by 20%. Conclusion H. pylori infection upregulates the expressions of Bax mRNA and protein in gastric cancer cell line SGC-7901, and induces activation of caspase-9 and -3. Mi- tochondrial pathway may be the major one in H. pylori-induced apoptosis in SGC-7901.