AMPK（AMP-activated protein kinase）是阿司匹林代谢产物水杨酸的一个靶标。AMPK作为细胞内重要的能量感受分子在恶性肿瘤中既可发挥抑癌作用，也可发挥促癌作用，并导致肿瘤对某些药物耐药。阿司匹林是一个有前景的肿瘤化学预防药物。本课题拟建立肝脏特异AMPKα1敲除小鼠模型，研究AMPK对二乙基亚硝胺/四氯化碳/乙醇诱导肝癌发生、发展的影响，并研究阿司匹林是否具有预防二乙基亚硝胺/四氯化碳/乙醇诱导肝癌的作用，以及AMPK对阿司匹林预防肝癌的影响。此外，我们还将结合AMPK敲除的肝癌细胞深入研究相关机制。明晰AMPK究竟主要发挥抑癌作用还是促癌作用将对抗肿瘤药物研发具有重要指导意义。 厘清AMPK对阿司匹林预防肝癌的影响的意义在于指导制定更合理、有效的肿瘤防治方案，亦即是否有将阿司匹林与AMPK靶向药物联合应用的必要性。

AMPK is a target of salicylate acid, the metabolite of aspirin. As an important energy sensor, AMPK has both anti-cancer and pro-tumor effects, and confers resistance to some drugs. Aspirin is a promising cancer chemopreventive agent. This project aims to develop liver-specific AMPK knockout mice model to investigate the effects of AMPK on DEN/CCl4/ethanol-induced hepatocarcinogenesis. in addition, we will investigate whether aspirin can prevent DEN/CCl4/ethanol-induced hepatocarcinogenesis, and how AMPK may affect the chemoprevention of hepatocarcinogenesis by aspirin. Furthermore, we will develop AMPK knockout hepatocarcinoma cell line to dissect the mechanisms underlyling the above-mentioned processes. The clarification of whether AMPK inhibits or promotes tumorigenesis is helpful for development of anti-cancer agents. Whether AMPK affects the prevention of liver cancer by aspirin may be a rationale for combination of aspirin and AMPK-targeted agents.