本文简要综述了近十多年来，本项目组探索金属硫蛋白家族（Metallothioneins，MTs）在肝癌发生与发展中的作用及其中医药防治机制。研究发现，MTs对于肝癌细胞恶性增殖是必要的，在不同应激状态下肝癌细胞MTs表达会显著增加，MTs可能通过上调肝癌细胞核糖体蛋白等基因的表达发挥促进其恶性增殖的作用。MTs在肝癌细胞中的过表达，可能直接改变了细胞核内离子的平衡，并通过与多基因的相互作用，发挥促进肝癌细胞恶性增殖基因表达的作用。中医药防治肝癌常用治法方药可以不同程度地减轻和缓解由二乙基亚硝胺（Diethylnitrosamine，DEN）所造成的肝毒性和损伤作用，降低MTs表达，提示在肝脏保护、抑制其异常增生和肝癌发展方面十分重要。

It is a brief review of our research on the role of metallothioneins(MTs)in the occurrence and development of hepatocellular carcinoma(Hcc)in more than a decade,and the mechanism of prevention and treatment for Hcc in the field of TCM.It was found that MTs were required for the malignant proliferation of Hcc cells and their expressions significantly increased under different levels of stress.MTs may exert their effects on promoting proliferation via increasing ribosomal protein gene or other gene expressions.The over-expressions of MTs directly altered the balance of ions in the cell nucleus,and interacted on the genes promoting malignant proliferation.Hepatotoxicity and hepatic damage caused by DEN were reduced and relieved to different extents by the representative formula or constitute,which under the common therapeutic principle,by which MTs expressions were down-regulated as well.In conclusion,both effects above are important in the liver protection,inhibition of hyperplasia and carcinogenesis.

国家自然科学基金委面上项目（81273641）：MTs在肝癌细胞应激反应中的作用及不同治法调节机制的研究，负责人：方肇勤；国家自然科学基金委面上项目（30973703）：若干中医治法下调基因沉默后肝癌细胞动力学基因表达谱分析，负责人：方肇勤；国家自然科学基金委面上项目（30672574）：采用RNAi检测若干与中医治法相关肝癌高表达新基因的作用，负责人：方肇勤；国家自然科学基金委面上项目（30271576）：不同治法对大鼠肝癌后基因组转录调控的进一步研究，负责人：方肇勤。