The Role of COX‐2 in Intestinal Cancer

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Abstract
Cyclooxygenase (COX), the key regulatory enzyme for prostaglandin synthesis is transcribed from two distinct genes. COX‐1 is expressed constitutively in most tissues, and COX‐2 is induced by a wide variety of stimuli and was initially identified as an immediate‐early growth response gene. In addition, COX‐2 expression is markedly increased in 85–90% of human colorectal adenocarcinomas, whereas COX‐1 levels remain unchanged. Several epidemiological studies have reported a 40–50% reduction in the risk of developing colorectal cancer in persons who chronically take such nonsteroidal anti‐inflammatory drugs (NSAIDs) as aspirin, which are classic inhibitors of cyclooxygenase. Genetic evidence also supports a role for COX‐2, since mice null for COX‐2 have an 86% reduction in tumor multiplicity in a background containing a mutated APC allele. These results strongly suggest that COX‐2 contributes to the development of intestinal tumors and that inhibition of COX is chemopreventative.