Cyclooxygenase-2 and Bcl-2 expression in the stomach mucosa of Wistar rats exposed to Helicobacter pylori, N'-methyl- N'-nitro- N-nitrosoguanidine and bile

Virchows Arch. 2002 Jul;441(1):77-84. doi: 10.1007/s00428-001-0571-z. Epub 2001 Dec 18.


Cyclooxygenase-2 (COX-2) and Bcl-2 have been implicated in upper gastrointestinal tract carcinomas, but the underlying mechanisms are not known. In the present study we assessed the correlation of COX-2 and Bcl-2 to known cell kinetics in the glandular stomach mucosa of 104 Wistar rats given combinations of Helicobacter pylori, MNNG ( N'-methyl- N'-nitro- N-nitrosoguanidine) and bile. COX-2 expression, Bcl-2 and cell proliferation (Ki-67) in antral and corpus mucosa were determined immunohistochemically. Apoptotic cells were detected using terminal uridine deoxynucleotidyl nick end labelling technique. Expression of COX-2 was found in the lower portion of glandular corpus epithelium, and Bcl-2 positivity was mainly seen in the proliferative zone of both antrum and corpus mucosa. COX-2 expression in histologically normal-appearing corpus mucosa was associated with cell proliferation, atrophy and intestinal metaplasia in antrum and with Bcl-2 expression in corpus mucosa. No correlation was found between apoptosis and Bcl-2 expression. MNNG but not H. pylori significantly increased COX-2 in corpus mucosa. H. pylori, however, promoted the COX-2 expression in corpus when bile was added and Bcl-2 expression in antrum. Abnormal expression of both COX-2 and Bcl-2 seem to be involved in H. pylori-induced gastric carcinogenesis by altering the gastric cell kinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bile / metabolism*
  • Cell Division / drug effects
  • Cyclooxygenase 2
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism*
  • Gastric Mucosa / microbiology
  • Gastric Mucosa / pathology
  • Helicobacter Infections / metabolism*
  • Helicobacter pylori*
  • Immunohistochemistry
  • Isoenzymes / biosynthesis*
  • Male
  • Methylnitronitrosoguanidine / toxicity*
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Rats
  • Rats, Wistar


  • Isoenzymes
  • Proto-Oncogene Proteins c-bcl-2
  • Methylnitronitrosoguanidine
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases