基于分子对接技术和网络药理学探索姜黄素治疗肝癌的分子机制  

The Molecular Mechanism of Curcumin in the Treatment of Liver Cancer Based on Molecular Docking Technology and Network Pharmacology

作　　者：俞天添 杨兴武[2] 王鑫[1] 王国泰[2] YU Tiantian;YANG Xingwu;WANG Xin;WANG Guotai(Shaanxi University of Traditional Chinese Medicine,Xianyang,Shaanxi,712000,China;The Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine,Xianyang,Shaanxi,712000,China)

机构地区：[1]陕西中医药大学,陕西咸阳712000 [2]陕西中医药大学第一附属医院,陕西咸阳712000

出　　处：《肿瘤药学》2021年第2期180-185,共6页Anti-Tumor Pharmacy

基　　金：咸阳市二〇一九年重点研发计划(2019K01-100)。

摘　　要：目的基于分子对接技术和网络药理学探索姜黄素治疗肝癌的分子作用机制。方法通过SuperPred、SwissTargetPrediction和NCBI、DisGeNET、GeneCards数据库分别检索姜黄素的作用靶点和肝癌疾病作用靶点,映射获得姜黄素治疗肝癌的潜在靶点。借助STRING数据库构建蛋白互作(PPI)网络,导入Cytoscape软件,按MCC计算法筛选核心靶点。将潜在靶点应用clusterProfiler R软件进行GO富集和KEGG通路分析。依托Zinc、PDB数据库获得姜黄素的分子结构及核心靶点蛋白结构,利用AutoDockTools、PyMOL软件,将二者进行预处理及分子对接。结果通过网络数据挖掘获得姜黄素作用靶点114个,肝癌疾病靶点1560个,映射获得37个姜黄素治疗肝癌的潜在靶点;PPI网络按MCC法计算后获得10个核心靶点互作关系;通过GO富集分析获得生物过程(BP)1061条,细胞组成(CC)18条,分子功能(MF)72条;通过KEGG通路分析获得56条信号通路,主要涉及PD-L1表达和PD-1检查点通路、肿瘤中的蛋白聚糖、乙型肝炎、病毒致癌作用、肿瘤中的miRNAs等;分子对接结果显示,姜黄素与核心靶点的结合能均<0 kJ·mol-1,其中TP53、EGRF、MMP9、ESR1、HIF1A、AR与姜黄素的结合能<-5 kJ·mol-1,结合活性显著。结论基于分子对接技术及网络药理学初步揭示姜黄素以多靶点、多通路、多生物学功能等特点发挥对肝癌的治疗作用,为后续研究提供了理论基础。Objective To explore the molecular mechanism of curcumin in the treatment of liver cancer based on molecular docking technology and network pharmacology. Methods The targets of curcumin and liver cancer were retrieved from the SuperPred, Swiss Target Prediction and NCBI, DisGeNET and GeneCards databases. The protein-protein interaction(PPI) network was constructed by STRING and visualized by Cytoscape software, and the hub targets were identified with the maximal clique centrality(MCC) algorithm. The R package clusterProfiler was used for GO enrichment and KEGG pathway analysis. With the help of AutoDockTools and PyMOL software, the hub targets were pretreated with curcumin and the molecular docking was conducted. Results A total of 114 targets of curcumin and 1560 targets of liver cancer were obtained, and 37 potential targets of curcumin in the treatment of liver cancer were mapped. Ten hub target interaction relationships were obtained by MCC algorithm. Through GO enrichment analysis, 1061 biological processes(BP), 18 cell components(CC) and 72 molecular functions(MF) were obtained. A total of 56 signaling pathways were obtained through KEGG pathway analysis, mainly involving PD-L1 expression and PD-1 checkpoint pathways, proteoglycans in cancer, hepatitis B, oncogenic effect of virus, microRNAs in cancer and other signaling pathways. The molecular docking results showed that the binding energies of curcumin with the hub targets were all < 0 kJ·mol-1, and the binding energies of curcumin with TP53, EGRF, MMP9, ESR1, HIF1A, and AR were all <-5 kJ·mol-1, showing significant binding activity. Conclusion Based on network pharmacology and molecular docking technology, curcumin is preliminarily revealed to play a therapeutic role in liver cancer with multi-target, multi-pathway and multi-biological functions, providing a theoretical basis for subsequent research.

关 键 词：分子对接 网络药理学 姜黄素 肝癌 分子机制 

分 类 号：R735.7[医药卫生—肿瘤]