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Helicobacter pylori infection induces apoptosis in gastric cancer cells through the mitochondrial pathway
Author(s) -
Zhang Hao,
Fang DianChun,
Lan ChunHui,
Luo YuanHui
Publication year - 2007
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2007.04959.x
Subject(s) - apoptosis , caspase , flow cytometry , helicobacter pylori , blot , microbiology and biotechnology , caspase 9 , cell culture , medicine , cancer research , biology , programmed cell death , biochemistry , gene , genetics
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.