原发性肝癌癌变机制的认识与阐明将为其治疗提供新的药物或手段。TRPM8属于瞬时受体电位家族成员，是位于细胞膜上的一类重要的阳离子通道超家族,其中TRPV 1（亦称辣椒素受体）可被内源性大麻素物质激活。我们已对大麻素及其受体﹑辣椒素及其受体在原发性肝癌中的作用进行了系统研究。而有关TRPV 2在原发性肝癌癌变作用的研究正在实施中。在此基础上，我们又发现TRPM8的表达与肝癌的分化相关。本项目拟在已有研究工作基础上通过整体及细胞水平探讨TRPM8在肝癌癌变中的生物学作用，从大麻素受体，TRPV，自噬，微环境，能量代谢以及相关信号传递等方面揭示其分子机制；并探索围绕TRPM8为靶点开发新的化疗药物的可能性，为原发性肝癌的治疗提供新的理论依据。本项目的特点与创新之处探索TRPM8在原发性肝癌中的分子作用机制，也是对以往国家自然科学基金项目的系统性拓展和进一步的补充。

The elucidation of the mechanisms on hepatocarcinogenesis can offer novel modalities for its treatment.TRPM8,a member of TRP family,is a cation channel on the cullular membrane.TRPV1 can be activated by endocannabinoid.We have already investigated that cannbinoid and its receptors﹑TRPV1 and TRPV2 take roles in hepatocarcinogenesis. Moreover,our recent study indentified that TRPM8 was overexpressed in HCC and correlated with dedifferentiation and portal vein involvement as well.This project aimed at analysis of TRPM8 on its biological potentials in HCC, including cannabinoid receptors, TRPV,autophagy,microenvironment,energetic metabolism and relevant signal transduction.The characteristics of the project are the exploration of TRPM8 on the molecular mechanisms in hepatocarcinogenesis and is also a systemic and further supplements of our previous projects granted by NSFC.