基于Akt/mTOR信号通路干预肿瘤细胞能量代谢异常的寒凉中药白头翁中皂苷类成分抗癌机制研究

项目名称： 基于Akt/mTOR信号通路干预肿瘤细胞能量代谢异常的寒凉中药白头翁中皂苷类成分抗癌机制研究

项目编号： No.81460618

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 陈兰英

作者单位： 江西中医药大学

项目金额： 49万元

中文摘要： Warburg 早在上世纪20年代就发现肿瘤代谢异常现象，为此1931 年获诺贝尔奖。直到2011年Weinberg在Cell上报道能量代谢异常是肿瘤细胞十大特征之一，又引起全球再次高度重视。这一特征表明，抑制肿瘤细胞糖酵解而切断肿瘤的营养从而饿死肿瘤，可能成为新的治疗手段。本课题组前期研究发现，寒凉中药白头翁中皂苷类成分对结肠癌能量代谢有调控作用，主要表现为能显著降低肿瘤细胞对葡萄糖消耗及乳酸产生，抑制糖酵解，减少ATP等；并能抑制HT-29细胞p-AKT、p-mTOR蛋白表达，且不同成分对相关调控基因影响也不同。因此，白头翁不同成分可能作用于Akt/mTOR信号通路不同靶点而达到协同抗肿瘤作用。基于此，本课题在前期基础上，拟通过结肠癌动物与细胞实验，利用分子生物学技术系统研究白头翁皂苷类成分对Akt/mTOR信号通路及各靶点作用特点，揭示白头翁总皂苷抗肿瘤多靶点综合效应机制。

中文关键词： Akt/mTOR信号通路；白头翁皂苷；抗癌；分子机制；肿瘤细胞能量代谢

英文摘要： Warburg found tumor tissue metabolic anomalies in the early 20 's and therefore won the Nobel Prize in 1931. When Robert and Weinberg reported that energy metabolism is one of the ten characteristics of tumor cells in the journal Cell once again in 2011, the feature of tumor cell metabolic anomalies has attracted a great deal of scholarly attention.This feature suggests that it could become the new means of treatment to inhibit glycolytic pathway of tumor cells and cut off the tumor's nutrition to starve tumor. Our previous studies have found that pulsatilla saponin had a regulating effect on energy metabolism of human colon cancer cell（HT-29）.It could significantly reduce the consumption of glucose ，lactic acid and ATP in order to inhibit glycolysis of cancer cell. It and its components also might inhibit p-AKT and p-mTOR protein expression of HT-29 differently, and different components have different effects on related genes expression.Our group study found that pulsatilla saponin constituents have a regulating effect on energy metabolism in colon cancer cell, and different ingredients might have different targets on regulation of AKT/mTOR signal pathway in order to achieve synergistic antitumor effect.Based on this, pulsatilla saponin and its components would be studied on AKT/mTOR signal pathway and related targets by the methods of molecular biology on colon cancer animal and cell experiment. It might clarify multi-target combined effect of anti-tumor mechanism of pulsatilla saponin components.

英文关键词： Akt/mTOR signaling pathways;pulsatilla saponin;anti-caner effect;molecular mechanism;energy metabolism of tumor cells