Abstract
Background: Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, may reduce the risk and mortality of certain types of human cancer. The chemopreventive effect of celecoxib on preneoplastic lesions induced by chemical hepatocarcinogenesis was investigated. Materials and Methods: Male Sprague Dawley rats were fed a celecoxib-supplemented diet between days 18 and 26 post-initiation (1500 ppm) and sacrificed on day 26. The effects of celecoxib on proliferation, apoptosis, COX-2 activity and liver function were evaluated by immunohistochemistry, TUNEL assay, enzyme-immunoassay and spectrophotometry, respectively. Results: Celecoxib decreased, in area and number, Á-glutamyltranspeptidase and glutathione S-transferase placental-positive lesions, below levels found after 18 days, by 55.2% and 62.2%, and by 50.5% and 71.1%, respectively, (p<0.05). Celecoxib neither induced apoptosis nor altered the levels of prostaglandin E2, bilirubin or alanine aminotransferase in the plasma; however, proliferating cell nuclear antigen and cyclin D1 decreased by 77.7% and 94.9%, respectively, (p<0.05). Conclusion: Celecoxib regresses existing preneoplastic liver lesions through antiproliferative processes, without altering liver function.
Footnotes
- Received November 25, 2005.
- Revision received February 1, 2006.
- Accepted February 9, 2006.
- Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved