原发性肝细胞癌中内源性大麻素的含量变化及其意义

Abstract

目的 检测并比较临床肝癌组织与相应癌旁组织中内源性大麻素及其相关受体、合成代谢酶的含量变化,为寻找肝癌新型标志物和治疗靶点提供依据。方法 采用HPLC-MS检测47例肝癌组织以及相应癌旁组织的内源性大麻素含量,采用RT-PCR和Western-blot法检测相关受体及合成代谢酶的mRNA、蛋白表达。结果 在肝癌组织中,内源性大麻素2-花生四烯酰甘油酯（2-AG）含量最高,且显著高于癌旁组织（P〈0.01）;内源性大麻素花生四烯酰乙醇胺（AEA）的含量最低,且显著低于癌旁组织（P〈0.05）。类内源性大麻素油酰乙醇胺（OEA）和棕榈酰乙醇胺（PEA）的含量在肝癌组织与癌旁组织中未检测到显著差异。肝癌组织中2-AG受体CB2的表达较癌旁组织显著上升（P〈0.05）;AEA受体CB1的表达则呈显著下降趋势（P〈0.05）。结论 肝癌组织中内源性大麻素系统发生了显著变化,提示2-AG高表达和AEA低表达可能对原发性肝细胞癌的形成和发展具有重要作用。

Objective To detect and analyze endocannabinoids and its related enzymes and their receptors in hepatocellular carcinoma（HCC）tissue and adjacent tissues in order to identify new markers and therapeutic targets for hepatocellular carcinoma HCC.Methods Endocannabinoids levels were detected by HPLC-MS in 47 cases of HCC and adjacent tissues.RT-PCR and Western-blot were used to detect the expression of genes and proteins of the related metabolism enzymes and receptors.Results The content of 2-AG,one of the representative endocannabinoids,was the highest in HCC tissues and was significantly higher than that in the adjacent tissues（P〈0.01）,while the content of AEA ws the lowest and was significantly lower than that in the adjacent tissues（P〈0.05）.There were no significant difference in the levels of other fatty acyl ethanolamines,such as OEA and PEA,between HCC and adjacent tissues.The expression of CB2,a receptor of 2-AG,was significantly increased in HCC tissues（P〈0.05）,while the levels of CB1,a receptor of AEA,was observed at a decreased trend（P〈0.05）.Conclusion There was a notable change in endocannabinoid system in HCC,which suggests that high expression of 2-AG and low expression of AEA may play an important role in the formation and development of HCC.