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.微阵列分析（Microarray analysis）是一种用于识别抗癌药物调控靶基因的有效研究方法。本研究在改良耐药肝细胞模型中评估了塞来昔布（celecoxib）对基因表达谱的影响。接受致癌处理的大鼠被喂食含有1500ppm塞来昔布的饲料。研究设计了两种塞来昔布给药方案：在进展给药方案中，塞来昔布于癌症诱导后第18天至第25天给药，共计8个治疗日，此时已明确形成的癌前病变开始出现；在启动给药方案中，塞来昔布于癌症诱导前1周至诱导后25天给药，共计32个治疗日。本研究设置仅接受致癌处理的大鼠组作为癌症阳性对照，并将所有组别大鼠的基因表达谱与未处理阴性对照组进行比较。通过对基因表达谱的分析，本研究成功鉴定出受塞来昔布调控的新型靶基因，并提出了塞来昔布化学预防肝细胞癌变的潜在作用机制。