Early experiments using
carcinogen-induced rat intestinal
tumor models demonstrated the inhibitory effects of non-steroidal anti-inflammatory drugs (
NSAIDs) on intestinal
tumorigenesis. Furthermore, epidemiological studies and clinical trials for
familial adenomatous polyposis (FAP) patients supported the possibility that
NSAIDs can be used as chemopreventive agents. The major target molecules of
NSAIDs are
cyclooxygenases (COX), which catalyze the rate-limiting step of
prostaglandin biosynthesis. Two
isoenzymes of COX have been identified: COX-1 and COX-2. Whereas COX-1 is expressed constitutively in most tissues and responsible for tissue homeostasis, COX-2 is inducible and plays an important role in
inflammation and
tumorigenesis. A genetic study using compound mutant mice of COX-2-/- and Apc delta 716, a model for human
familial adenomatous polyposis (FAP), directly demonstrated that induction of COX-2 is critical for
intestinal polyp formation. Numerous studies have also demonstrated that COX-2-selective inhibitors suppress
intestinal polyp formation in Apc gene-mutant mice and xenografted
cancer cell growths. In addition, stimulation of angiogenesis is one of the major effects by COX-2 expression that is induced in the
polyp stromal cells. These data from animal model studies should be helpful in understanding the in vivo mechanism(s) of
tumor suppression by
NSAIDs or
COX-2 inhibitors. Here, we review the animal studies that reported the suppression of intestinal
tumor growths by
NSAIDs or
COX-2 inhibitors.