Celecoxib induces regression of putative preneoplastic lesions in rat liver.
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.


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, gamma-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).


CONCLUSIONS
Celecoxib regresses existing preneoplastic liver lesions through antiproliferative processes, without altering liver function.
Arellanes-Robledo
Jaime
J
Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav), Av. IPN No. 2508. Col. San Pedro Zacatenco, C.P. 07360, México, DF.
Márquez-Rosado
Lucrecia
L
Pérez-Carreón
Julio Isael
JI
Fattel-Fazenda
Samia
S
Aguirre-García
Jesús
J
Villa-Treviño
Saúl
S
D000818:Animals; D000068579:Celecoxib; D048708:Cell Growth Processes / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000097:blood; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone