基于药物和靶点网络的淫羊藿抗肿瘤作用机制研究

Traditional Chinese medicines (TCMs) have shown significant curative effects in treating complex diseases such as cancer. However, due to the “multi-components”, “multi-targets” and “multi-pathways” features of TCMs, the pharmacodynamic basis and mechanisms of action of most TCMs are still unclear. In this project, we take Epimedium as an example, and study its anti-tumor mechanism of action from theoretical calculations and biological experiments. Firstly, using various network pharmacology, bioinformatics and chemical genomics methods, a systemic research framework technology for Epimedium which integrated drug ADME screening, target prediction, network construction, pathway enrichment and drug-disease correlation analysis, was developed. Based on this technology, the potential active ingredients of Epimedium were screened and their corresponding targets were identified. Then, the drug-target network was constructed and functionally modularized, and key targets in the net were selected for further GO and pathway enrichment analysis. Subsequently, molecular dynamics, binding free energy, and in vitro experiments were used to comfirm the target of key components. Finally, the anti-tumor mechanism of Epimedium was systematically studied by in vivo experiments and Western blotting from different levels of whole animals, tissues and molecular proteins. The successful development of this project provides a new framework for the study of anti-tumor mechanisms of TCMs, and also offers a new approach for humans to explore drug interventions for complex diseases.

中药在许多复杂疾病诸如癌症的治疗上呈现出显著的疗效，但因其多成分、多靶点和多通路的特征，导致大多数中药的药效物质基础和分子作用机制仍不清楚。本项目以淫羊藿为例，从理论计算和生物实验两方面对其抗肿瘤机制进行了研究。首先，借助网络药理学、生物信息学和化学基因组学等方法构建一套集成药物ADME筛选、靶点识别、网络构建、通路富集和药-病关联分析的淫羊藿抗肿瘤系统性研究框架技术，以此来获得其潜在的活性成分和作用靶标；接着，构建药物-靶点网络，并对其进行功能模块化分析，选择关键靶点进行GO和通路富集分析；随后，应用分子动力学、结合自由能和离体实验对关键成分的靶点进行验证；最后，用在体实验和蛋白印迹等方法，从整体动物、组织器官和分子蛋白不同水平系统地研究了淫羊藿的抗肿瘤作用机制。本项目的成功开展为中药的抗肿瘤机制研究提供了一个新框架，也为人类探索复杂疾病的药物干预提供了一种新方法。

中药在许多复杂疾病诸如癌症的治疗上呈现出显著的疗效，但因其多成分、多靶点和多通路的特征，导致大多数中药的药效物质基础和分子作用机制仍不清楚。本项目以淫羊藿为例，从理论计算和生物实验两方面对其抗肿瘤机制进行了研究。首先，借助网络药理学、生物信息学和化学基因组学等方法构建一套集成药物ADME筛选、靶点识别、网络构建、通路富集和药-病关联分析的淫羊藿抗肿瘤系统性研究框架技术，以此来获得其潜在的活性成分和作用靶标；接着，构建药物-靶点网络，并对其进行功能模块化分析，选择关键靶点进行GO和通路富集分析；随后，应用分子动力学、结合自由能和离体实验对关键成分的靶点进行验证；最后，用在体实验和蛋白印迹等方法，从整体动物、组织器官和分子蛋白不同水平系统地研究了对淫羊藿的抗肿瘤作用机制。本项目以淫羊藿为例构建了一个新的中药研究体系，并且成功的应用于中药复方及其单体的机制研究上。此外借助新的方法体系，我们还发现了新的肿瘤标志物，并应用于中药抗肿瘤的研究中。本项目已发篇论文7篇，其中SCI论文5篇。本项目已经发篇论文7篇，其中SCI论文5篇。本项目的成功开展为中药的抗肿瘤机制研究提供了一个新框架，也为人类探索复杂疾病的药物干预提供了一种新方法。