Helicobacter pylori infection induces apoptosis in gastric cancer cells through the mitochondrial pathway.
OBJECTIVE
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-7,901 were co-cultured with H. pylori NCTC 11,637, 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-7,901 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-7,901 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-7,901 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.
Zhang
Hao
H
Department of Gastroenterology, South-west Hospital, Third Military Medical University, Chongqing, China.
Fang
Dian-Chun
DC
Lan
Chun-Hui
CH
Luo
Yuan-Hui
YH
D000230:Adenocarcinoma / Q000382:microbiology* / Q000473:pathology*; D017209:Apoptosis; D053148:Caspase 3 / Q000502:physiology*; D053453:Caspase 9 / Q000502:physiology*; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D053148:Caspase 3; D053453:Caspase 9