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KMID : 0603519990040040213
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Journal of Korean Association of Cancer Prevention
1999 Volume.4 No. 4 p.213 ~ p.221
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Chemopreventive Effects of Nonsteroidal Antiinflammatory Drugs (NSAIDs)
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Park Min-Seon
Min Byung-Re
Nam Myeong-Jin
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Abstract
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Nonsteroidal antiinflammatory drugs (NSAIDs) have considerable potential as chemopreventive agents for corolectal cancer. Recent case-control drug surveillance and large cohort studies found that patients with regular aspirin use had a reduced incidence of colorectal cancer and/or decreased death rate from this disease. Several different NSAIDs reduce formation of both colon adenomatous polyps (the precusor lesion of colon cancer) and cancers in experimental animals given known carcinogen. Perhaps most convincing are reports that the NSAID, sulindac promotes regression and inhibits recurrence of adenomatous colon polyps in patients with Familial adenomatous polyposis. The best characterized pharmacological effect of the NSAIDs is their reduction of prostaglandin synthesis by inhibiting prostaglandin synthetase, which catalyzes the formation of prostaglandin precursors from arachidonic acid. Several lines of evidence are contrary to the concept that inhibition of prostaglandin synthesis is central to the NSAIDs’ chemopreventive effects. Relatively high levels of prostagalndins have been reported to inhibit tumor cell growth both in vitro and in vivo, and to inhibit differentiation in some tumor cell lines. Some of the data reviewed here indicate that COX inhibition by NSAIDs is indeed required for their chemopreventive effect. However another body of data make the equally strong case that COX inhibiton is not required for certain presumed chemopreventive effects of NSAIDs. This multiplicity of NSAIDs, if confirmed, could in fact explain their high degree of effectiveness in colon cancer prevention in humans. The great challenge will be to determine which of these or other yet unknown mechanisms produced the remarkable anticancer effect of NSAIDs, as well as the relative contribution of each. If and when these key questions are worked out, then a great deal will have learned about colorectal carcinogenesis.
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KEYWORD
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Nonsteroidal antiinflammatory drugs (NSAIDs), Colorectal cancer, Cyciooxygenase (COX), Prostaglandin (PGs)
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