基于反向分子对接网络药理学探讨去甲斑蝥素治疗肝癌机制

Mechanism of Norcantharidin in the Treatment of Liver Cancer Based on Reverse Molecular Docking Network Pharmacology

目的:基于反向分子对接网络药理学探讨去甲斑蝥素(NCTD)治疗肝癌(HCC)的关键靶点及作用机制。方法:在ZINC数据库检索“Norcantharidin”获得化合物结构,PharmMapper反向对接预测靶点;Drugbank、OMIM、GeneCards数据库获得肝癌靶点;绘制韦恩图获取交集基因;凭借STRING平台分析NCTD治疗肝癌的靶点,利用Cytoscape 3.7.1可视化构建“成分—靶点—疾病”网络图,经Network Analyzer分析靶点网络拓扑参数提取关键靶点,利用MCODE插件进行模块分析;David做富集分析,并构建“成分疾病—靶点—通路”网络筛出关键基因。结果:获得交集靶点101个,103个分子功能和144条KEGG通路。结论:核心靶点有IGF1、AKT1、HRAS、EGFR、MAPK1,核心通路有癌症通路、PI3K-Akt信号通路、癌症中蛋白聚糖通路、MAPK信号通路、Ras信号通路、前列腺癌通路、化学致癌受体激活通路、肝细胞癌通路。NCTD通过多靶点、通路联合治疗肝癌。

Objective:To explore the key targets and mechanism of Norcantharidin(NCTD)in the treatment of hepatocellular carcinoma(HCC)based on reverse molecular docking network pharmacology.Methods:The compound structure was obtained by searching“Norcantharidin”in ZINC database,and the target was predicted by PharmMapper reverse docking.Drugbank,OMIM,GeneCards database for liver cancer targets;drawing Venn diagram to obtain intersection genes;the STRING platform was used to analyze the targets of NCTD in the treatment of liver cancer.Cytoscape 3.7.1 was used to visually construct the“component-target-disease”network diagram.The network topology parameters of the target network were analyzed by Network Analyzer to extract the key targets,and the MCODE plug-in was used for module analysis.David performed enrichment analysis and constructed a“component-target-pathway”network to screen out key genes.Results:101 intersection targets,103 molecular functions and 144 KEGG pathways were obtained.Conclusion:The core targets include IGF1,AKT1,HRAS,EGFR and MAPK1.The core pathways include cancer pathway,PI3K-Akt signaling pathway,proteoglycan pathway in cancer,MAPK signaling pathway,Ras signaling pathway,prostate cancer pathway,chemical oncogenic receptor activation pathway and hepatocellular carcinoma pathway.NCTD treats liver cancer through multiple targets and pathways.