title: Helicobacter pylori infection induces apoptosis in gastric cancer cells through the mitochondrial pathway.
abstract: 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.
authors.affiliation: Department of Gastroenterology, South-west Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Dian-Chun
authors.initials: DC
authors.lastname: Fang
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: Lan
authors.forename: Yuan-Hui
authors.initials: YH
authors.lastname: Luo
mesh_terms: 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
chemical_list: D053148:Caspase 3; D053453:Caspase 9