Helicobacter pylori infection induces apoptosis in gastric cancer cells through the mitochondrial pathway.

Background and Aims:  To clarify the role of the mitochondrial pathway in apoptosis induced by H. pylori infection in gastric epithelial cells. Methods:  Cells of a gastric adenocarcinoma cell line SGC-7901 were co-cultured with H. pylori NCTC 11637, with or without preincubation with the inhibitors of caspases -3, -8, and -9. Apoptosis was determined by flow cytometry. RT-PCR was used to determine the expression of Bid, Bax, and Bcl-2 mRNA, and Western blotting was used to determine the expression of Bid, Bax, and Bcl-2 proteins, and the activation of caspases -3 and -9. Results: H. pylori directly induced apoptosis in SGC-7901 cells. Apoptotic indices (AIs) were 6.30 ± 0.40%, 11.57 ± 0.78%, 8.63 ± 0.67%, and 7.22 ± 0.97%, respectively, at 6, 12, 24, and 48 h after SGC-7901 cells were co-cultured with H. pylori. H. pylori up-regulated the expression of Bid and Bax at both protein and mRNA levels, and induced a time-dependent activation of caspases -3 and -9. Apoptosis was inhibited significantly by the preincubation of SGC-7901 cells with the inhibitors of caspase-3 (AIs were 1.72 ± 0.59%, 2.97 ± 0.55%, 4.38 ± 1.56%, and 3.29 ± 0.83%, respectively, at 6, 12, 24, and 48 h), and caspase -9 (AIs were 2.47 ± 0.53%, 6.68 ± 0.47%, 5.97 ± 0.46%, and 5.43 ± 0.15%, respectively, at 6, 12, 24, and 48 h). The caspase-8 inhibitor also reduced H. pylori-induced apoptosis by 20%. Conclusions: H. pylori infection induces apoptosis and the activation of caspases -3 and -9 in gastric cancer cells. Moreover, the caspase inhibitors significantly suppress H. pylori-induced apoptosis. These findings suggest that the mitochondrial pathway may be the major pathway in H. pylori-induced apoptosis in gastric epithelial cells.