Anti-Helicobacter pylori therapy followed by celecoxib on progression of gastric precancerous lesions

World J Gastroenterol. 2009 Jun 14;15(22):2731-8. doi: 10.3748/wjg.15.2731.


Aim: To evaluate whether celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, could reduce the severity of gastric precancerous lesions following Helicobacter pylori (H pylori) eradication.

Methods: H pylori-eradicated patients with gastric precancerous lesions randomly received either celecoxib (n = 30) or placebo (n = 30) for up to 3 mo. COX-2 expression and activity was determined by immunostaining and prostaglandin E(2) (PGE(2)) assay, cell proliferation by Ki-67 immunostaining, apoptosis by TUNEL staining and angiogenesis by microvascular density (MVD) assay using CD31 staining.

Results: COX-2 protein expression was significantly increased in gastric precancerous lesions (atrophy, intestinal metaplasia and dysplasia, respectively) compared with chronic gastritis, and was concomitant with an increase in cell proliferation and angiogenesis. A significant improvement in precancerous lesions was observed in patients who received celecoxib compared with those who received placebo (P < 0.001). Of these three changes, 84.6% of sites with dysplasia regressed in patients treated with celecoxib (P = 0.002) compared with 60% in the placebo group, suggesting that celecoxib was effective on the regression of dysplasia. COX-2 protein expression (P < 0.001) and COX-2 activity (P < 0.001) in the gastric tissues were consistently lower in celecoxib-treated patients compared with the placebo-treated subjects. Moreover, it was also shown that celecoxib suppressed cell proliferation (P < 0.01), induced cell apoptosis (P < 0.01) and inhibited angiogenesis with decreased MVD (P < 0.001). However, all of these effects were not seen in placebo-treated subjects. Furthermore, COX-2 inhibition resulted in the up-regulation of PPARgamma expression, a protective molecule with anti-neoplastic effects.

Conclusion: H pylori eradication therapy followed by celecoxib treatment improves gastric precancerous lesions by inhibiting COX-2 activity, inducing apoptosis, and suppressing cell proliferation and angiogenesis.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis / drug effects
  • Celecoxib
  • Cell Proliferation
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors* / pharmacology
  • Cyclooxygenase 2 Inhibitors* / therapeutic use
  • Disease Progression
  • Helicobacter Infections / complications
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori / drug effects*
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Middle Aged
  • Neovascularization, Pathologic
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Placebos
  • Precancerous Conditions / drug therapy*
  • Precancerous Conditions / microbiology
  • Precancerous Conditions / pathology
  • Pyrazoles* / pharmacology
  • Pyrazoles* / therapeutic use
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / etiology
  • Stomach Neoplasms / microbiology
  • Stomach Neoplasms / pathology
  • Sulfonamides* / pharmacology
  • Sulfonamides* / therapeutic use


  • Cyclooxygenase 2 Inhibitors
  • Ki-67 Antigen
  • PPAR gamma
  • Placebos
  • Pyrazoles
  • Sulfonamides
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Celecoxib