Chemoprevention of the hepatocarcinogenesis by celecoxib

Microarray analysis is a useful methodology to identify target genes modulated by anticancer drugs. Here, celecoxib effect on gene expression profiles was evaluated in the modified resistant hepatocyte model. Animals subjected to carcinogenic treatment were fed with diet containing 1500 ppm of celecoxib. Two schemes of celecoxib administration were designed. In the progression protocol, celecoxib was administrated between days 18 and 25 post-cancer initiation, a total of 8 celecoxib treatment days, when well established preneoplastic lesions starts to appear. In the initiation protocol, celecoxib was administrated from one week before until 25 days after of cancer initiation, a total of 32 celecoxib treatment days. A rat group was subjected only to the carcinogenic treatment as cancer positive control. Gene expression profiles of all groups were compared to a negative untreated control. The evaluation of gene expression profiles permitted us to identify new target genes that are modulated by celecoxib treatment. A possible mechanism of celecoxib chemoprevention of hepatocarcinogenesis is proposed. 9 weeks old Sprague Dawley rats, 4 rats per group, were subjected to Semple-Roberts' modified hepatocarcinogenesis protocol and sacrificed 25 days post-initiation. In celecoxib-treated groups, celecoxib was administrated mixed in diet at 1500 ppm. Negative and positive cancer progression controls were included to compare gene expression profiles. Microarray analysis was performed on liver samples, one replicate per rat, using dye swap.