汉防己甲素是从中草药中提取一种双苄基异喹啉类生物碱，在消炎、镇痛、肝纤维化和硒肺等方面都有较好疗效。近年来其抗肿瘤活性引起了人们的极大关注。我们研究发现较高浓度的汉防己甲素（30 μM）在体内、体外可通过激活ROS/Akt信号通路诱导肝癌细胞凋亡（Int J Cancer, 2011）。本项目研究发现，较低浓度的汉防己甲素（5 μM）不影响细胞存活，但能显著诱导肝癌细胞自噬，激活胞内部分MAPK（ERK和p38）激酶活性，促进自噬相关基因Atg-5和Atg-7的蛋白表达水平，但汉防己甲素诱导肝癌细胞自噬在其抗肿瘤治疗中的作用仍不清楚，本项目将在现有工作基础之上，研究汉防己甲素诱导肝癌细胞自噬的分子机理，阐述诱导癌细胞自噬与凋亡的关系，揭示细胞自噬对肿瘤生存的作用及其在抗肿瘤治疗中的意义，研究结果将为汉防己甲素在现代医学中的进一步开发应用、研制新的高效低毒的抗癌药物提供理论依据。

Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the broadly used Chinese medicinal herb Stephaniae tetrandrae, exhibits potent effects on treating inflammation, analgesia, hepatic fibrosis and even silicosis. Recently, its potential to be used as a cancer chemotherapeutic agent has aroused widespread concerns. We previously reported that a higher concentration of tetrandrine (30 μM) induce ROS/Akt mediated apoptosis in liver cancer cells in vitro and in vivo. In this project, we found that lower dose of tetrandrine (5 μM) has little effect on liver cancer cell viability but can prominently promote liver cancer cell autophagy by activating MAPK protein family member ERK, p38 and autophagic associated gene (Atg) protein family members Atg-5 and Atg-7 activities respectively. However it is unclear currently that the function of autophagy-inducing effect of tetrandrine and its anticancer application. With the basis of our previous investigation, we will further our project on aspects about unraveling the exact molecular mechanism of tetrandrine's autophagic inducing effect on hepatocellular carcinoma, displaying the relationship between tetrandrine induced autophagy and apoptosis and, finally, demonstrating the function of autophagy on tumorigenesis and its application on cancer treatment. We confidently believe that our research results will contribute to the development and clinical application of tetrandrine in modern medicine community and will provide the academic grounds for designing novel anticancer drugs with low cytotoxicity.