Clinical Significance of Prostaglandin E Synthase Expression in Colorectal Cancer

Introduction Nonsteroidal Anti-inflammatory Drugs and Colorectal Neoplasm Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the incidence of carcinogen-induced colon tumors in rodents and are associated with a reduced incidence of gastrointestinal cancer in epidemiological studies. NSAIDs inhibit prostaglandin endoperoxide synthase/cyclooxygenase (COX), the ratelimiting enzyme catalyzing the metabolism of arachidonic acid into prostaglandins (PGs), prostacyclin, and thromboxanes (Fig. 1). There are two isoforms of COX：a constitutively produced COX-1 and an inducible COX-2. Several lines of evidence indicate that the anti-neoplastic effect of NSAIDs is attributable to COX-2 inhibition. Selective COX-2 inhibitors reduce the incidence, multiplicity, and size of colonic carcinomas in the azoxymethane rat model, and their effectiveness against human colorectal neoplasms has been shown in epidemiological studies. Thus, COX-2 has received much attention as a molecular target for colorectal cancer prevention and treatment. Localization of COX-2 in Colorectal Neoplasms We have previously examined COX-2 expression in human colorectal neoplasm (adenoma and adenocarcinoma) tissues by immunohistochemical analysis.