Nonsteroidal antiinflammatory drugs could reverse Helicobacter pylori-induced apoptosis and proliferation in gastric epithelial cells

Dig Dis Sci. 1998 Sep;43(9):1957-63. doi: 10.1023/a:1018830408397.


It remains controversial whether the harmful effects of Helicobacter pylori (Hp) and nonsteroidal antiinflammatory drugs (NSAIDs) are additive. We studied the effects of Hp (virulent and nonvirulent strains) and NSAIDs, alone or in combination, on apoptosis and proliferation of gastric epithelial cells in nonulcer dyspepsia (NUD) patients. Forty-four (25 Hp-positive and 19 Hp-negative) consecutive Chinese NUD patients with rheumatoid arthritis who had taken continuously NSAIDs for more than three months were recruited for this study. Another 41 (20 Hp-positive and 21 Hp-negative) NUD patients not on any NSAIDs were included as controls. All patients underwent a gastroscopy examination and gastric biopsies. Hp infection was confirmed by CLOtest, anti-Hp ELISA, and [13C]urea breath test. The CagA status was determined by the anti-CagA antibody assay. The degree of gastritis, apoptosis, and proliferation indices were determined with H&E staining, terminal uridine deoxynucleotidyl nick end-labeling (TUNEL), and proliferating cell nuclear antigen (PCNA) immunostaining methods, respectively. A significantly higher apoptosis was observed in subjects who had Hp infection or had been consuming NSAIDs when compared with the controls. Unlike NSAID-treated subjects, patients with Hp infection were shown to have significantly enhanced cell proliferation. However, the increased apoptosis and proliferation in Hp-positive subjects were reversed by also taking NSAIDs. No correlation was found between apoptosis and proliferation in all the study groups. There was no association found between CagA expression or degree of gastritis with cell proliferation or apoptosis. It was demonstrated at the cellular level that NSAIDs could abrogate apoptosis or proliferation effects induced by Hp. Furthermore, the latter effects appeared not to be influenced by the virulent nature of the Hp strains.

Publication types

  • Clinical Trial

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Apoptosis / drug effects*
  • Cell Division / drug effects
  • Chronic Disease
  • Dyspepsia / drug therapy*
  • Dyspepsia / microbiology
  • Dyspepsia / pathology
  • Female
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / microbiology
  • Gastric Mucosa / pathology*
  • Gastritis / drug therapy*
  • Gastritis / microbiology
  • Gastritis / pathology
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology
  • Helicobacter pylori*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal