Inhibitory effect of etodolac, a selective cyclooxygenase-2 inhibitor, on stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbils

Hirohito Magari, Yasuhito Shimizu, Ken Ichi Inada, Shotaro Enomoto, Tatsuji Tomeki, Kimihiko Yanaoka, Hideyuki Tamai, Kenji Arii, Hiroya Nakata, Masashi Oka, Hirotoshi Utsunomiya, Yutaka Tsutsumi, Tetsuya Tsukamoto, Masae Tatematsu, Masao Ichinose

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29 Citations (Scopus)

Abstract

The effect of the selective COX-2 inhibitor, etodolac, on Helicobacter pylori (Hp)-associated stomach carcinogenesis was investigated in Mongolian gerbils (MGs). Hp-infected MGs were fed for 23 weeks with drinking water containing 10 ppm N-methyl-N-nitrosourea. They were then switched to distilled water and placed on a diet containing 5-30 mg/kg/day etodolac for 30 weeks. We found that etodolac dose-dependently inhibited the development of gastric cancer, and no cancer was detected at a dose of 30 mg/kg/day. Etodolac did not affect the extent of inflammatory cell infiltration or oxidative DNA damage, but it significantly inhibited mucosal cell proliferation and dose-dependently repressed the development of intestinal metaplasia in the stomachs of Hp-infected MGs. These results suggest that COX-2 is a key molecule in inflammation-mediated stomach carcinogenesis and that chemoprevention of stomach cancer should be possible by controlling COX-2 expression or activity.

Original languageEnglish
Pages (from-to)606-612
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume334
Issue number2
DOIs
Publication statusPublished - 26-08-2005

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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