ABSTRACT
Targeted inhibition of COX-2 is thus regarded as an effective and promising strategy for cancer prevention or treatment. This strategy is further supported by many epidemiologic and clinical studies in which long-term use of NSAID, such as aspirin and sulindac, was associated with a reduced risk of developing several malignant tumors including colorectal cancer (1,2,19). Because conventional NSAID inhibit not only COX-2 but also the housekeeping enzyme COX-1, responsible for maintaining the cellular homeostasis, these drugs may exert some deleterious side effects, which limits their long-term use. Therefore, selective COX-2 inhibitors have become most attractive in terms of chemopreventive as well as therapeutic potential (20). In human prostate cancer cells, the selective COX-2 inhibitor celecoxib induced apoptosis by blocking activation of the antiapoptotic Akt/protein kinase B, which was independent of Bcl-2 (21). Celecoxib also inhibits experimentally induced mammary (22), colon (23), bladder (24), and skin (25) carcinogenesis. In a recent randomized, double-blind, placebo-controlled intervention trial, twice daily intake of celecoxib at 100 or 400 mg for 6 mo significantly reduced the number of precancerous polyps and the total polyp burden in patients with familial adenomatous polyposis who are genetically susceptible to colorectal carcinogenesis (26).
