基于STAT-3靶点的泽兰属两种外来入侵植物抗肝癌药效物质基础及作用机理研究

肝癌是常见恶性肿瘤，STAT-3靶点在肝癌中高表达，在肿瘤组织产生、侵袭和转移中起关键作用，是研究肝癌药物新方向。泽兰属飞机草和紫茎泽兰两植物是入侵我国的毒草，据“化学武器”假说，入侵物种产生强生物毒素或化感物质，提示可能将是开发细胞毒性药物新资源。前期发现其环己烷和乙酸乙酯提取物对肝癌细胞株和STAT-3显强活性，从飞机草环己烷提取物中分离的13个萜类与黄酮类，采用MTT和STAT-3初筛显示化合物均对HepG2有强增殖抑制性。本研究拟分离更多化合物，阐明抗肝癌构效关系，发现关键药效团与STAT-3蛋白作用程度，更好发现两植物抗肝癌活性成分，并对活性提取物放大制备，采用MTT、STAT-3靶点筛选抗肝癌活性成分，应用计算机辅助药物设计研究构效关系及其与靶蛋白的作用，运用动物模型评价体内抗肝癌效果，从分子-细胞-动物水平上阐明两种植物的物质基础和作用机理，为肝癌防治和入侵植物开发提供依据。

Liver cancer is a common malignant tumor. The target of STAT-3 can be highly expressed in hepatocellular carcinoma, and plays a key role in tumor tissue of hepatocellular carcinoma, invasion and metastasis, which is a new direction in the research of liver cancer drugs. The Eupatorium odoratum and E. adenophorum, as two kinds of genus Eupatorium, have becomed the invasion of poisonous weeds. According to the "chemical weapons" hypothesis, invasive species can produce strong biological toxins or allelochemicals, suggesting that this phenomenon may be the development of new resources of cytotoxic drugs. We found that the two invasive plants of cyclohexane extract and ethyl acetate extract in hepatocellular carcinoma cell lines and STAT-3 protein,and showed strong activity in the early stage. We then focus on cyclohexane extracts of E. odoratum, 13 terpenes and flavonoids were isolated and purified. These compounds have been used MTT and STAT-3 technology for activity screening test, and they were found to have strong inhibitory activity of HepG2.. The project's research program, first of all, will be separated more compounds, and analysis of the relationship between the structure and efficacy of these compounds. Second, to analyze the relationship between the key parts of the active fractions and the STAT-3 protein, to better find two kinds of plant anti liver cancer active ingredients. Third, the project intends to use computer aided drug design technology, study on the relationship between the structure and effect of the compounds. Finally, an experimental animal model will be used to evaluate the effect of anti liver cancer in vivo. The research purpose is through from molecules to the cell level, from the cell to the animal level, to clarify the material basis and the effect of two kinds of plant invasion mechanism, promote the level of prevention and treatment of liver cancer, promote the development of new drugs from invasive plants.