The role of COX-2 and the effect of COX-2 antagonist on the progression of intestinal metaplasia and gastric cancer

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The aim of this study was to see whether administration of celecoxib, a selective COX-2 inhibitor, prior to the appearance of intestinal metaplasia could prevent the development of gastric cancer in Helicobacter pylorrinfected Mongolian gerbils. The incidence of gastric adenocarcinoma was : controls, 0% (0/10) ; H. pylori group, 65% (13/20), and H. pylori plus celecoxib group, 23% (5/22 ; p < 0.05). Continuous celecoxib administration significantly reduced COX activity and COX-2 protein expression, Cdx2 and MUC2 protein immunoreactivity, and the extent of Alcian blue periodic acid-Schiff-positive intestinal metaplasia in H. pylori-infected gerbils. Celecoxib also induced apoptosis in these gerbils. Significant inhibition of Cdx2 expression in celecoxib group was also shown by Western blot analysis. Prior to the first appearance of intestinal metaplasia, timely administration of celecoxib prevents gastric cancer occurrence by disrupting the progression of intestinal metaplasia into gastric carcinoma through its inhibition of Cdx2 expression in H. pylori-infected Mongolian gerbils.