Celecoxib Prevents Gastric Cancer In Mongolian Gerbils

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 23 Apr 2007 - 0:00 PDT

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This study, published in the journal "Digestion", investigated whether administration of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, prior to the appearance of intestinal metaplasia could prevent the development of gastric cancer in Helicobacter pylori-infected Mongolian gerbils.

Fifty-two Mongolian gerbils were divided into 3 groups and given 5 biweekly doses of N-methyl-N-nitrosourea (30 ppm). At week 12, group 2 (n = 20) and group 3 (n = 22) gerbils were then given an injection of H. pylori, while group 1 controls (n = 10) received Brucella broth alone. In addition, 7 weeks after H. pylori inoculation, at week 19, group 3 gerbils also received a 36-week administration course of celecoxib (1,500 ppm) in their diet. The incidence of gastric adenocarcinoma was determined at week 54 by histological analysis. COX-2 and Cdx2 protein expression and COX activity were evaluated for each group. The extent of intestinal metaplasia, Cdx2 and mucin 2 expression, and the apoptotic index were evaluated semi-quantitatively by immunohistochemistry.

The incidence of gastric adenocarcinoma was: group 1, 0% (0/10); group 2, 65% (13/20), and group 3, 23% (5/22; p < 0.05). Continuous celecoxib administration significantly reduced COX activity and COX-2 protein expression, Cdx2 and mucin 2 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 group 3 gerbils was also shown by Western blot analysis.

The study shows that 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 N-methyl-N-nitrosourea-pretreated H. pylori-infected Mongolian gerbils.

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