Numerous studies have also demonstrated that COX-2 selective inhibitors suppress intestinal polyp formation in Apc gene-mutant mice, and xenografted cancer cell growths.
The relationship between COX-2 and colon cancer is further confirmed by studies using the murine models of adenomatous polyposis coli, in which NSAIDs and gene knockouts reduce the number of spontaneously developing intestinal polyps.
COX-2 is overexpressed in adenomas and colorectal cancers, and COX-2-specific inhibitors have been shown to inhibit intestinal polyps in Apc(Delta716) mice more effectively than dual COX-1/COX-2 inhibitors such as sulindac.
While the exact mechanism(s) for this antitumor activity of p-XSC remains to be elucidated, it appears that modulation of beta-catenin expression and COX-2 activity is associated with inhibition of intestinal polyps.
Introduction of a COX-2 gene mutation, or feeding with the COX-2-selective inhibitor to the Apcdelta716 knockout mice, reduced the number and size of intestinal polyps dramatically.