摘要
目的:预测三七主要活性成分治疗肝细胞癌的作用靶点,探讨其多成分-多靶点-多通路的作用机制。方法:通过TCMSP数据库筛选三七的主要活性成分,并利用SEA数据库预测上述成分的潜在作用靶点;从人类基因组注释(Genecards)数据库获得肝细胞癌相关靶点;利用Venn软件对两者取交集获得三七治疗肝细胞癌的作用靶点。使用Cytoscape3.7.1软件构建有效成分-靶点网络。应用R语言软件包clusterProfiler对上述靶点进行基因本体论(gene ontology,GO)与代谢通路(metabolic pathway,KEGG)富集分析。结合BioGrid、InWeb_IM、OmniPath数据库构建靶点蛋白相互作用(target protein interaction,PPI),由Cytoscape软件进行可视化并进行网络拓扑分析以获得核心靶点。利用SYBYL-X2软件对核心靶点和对应活性成分进行分子对接验证结合强度。结果:共获得槲皮素、β-谷甾醇、豆甾醇、人参皂苷rh2等7个主要活性成分,可作用于肝细胞癌相关的32个靶点;这些靶点显著富集于核受体活性、转录因子活性,直接配体调节序列特异性DNA结合、类固醇激素受体活性、癌症中的蛋白多糖、EGFR酪氨酸激酶抑制剂耐药等多个GO和KEGG条目。结论:三七治疗肝细胞癌作用体现了中药多成分、多靶点、多通路的特点,为三七有效成分的筛选及深入研究提供一定科学依据。
Objective: To predict the target of the active components of Panax notoginseng in treatment of hepatocellular carcinoma,and to explore its multi-component-multi-target-multi-path mechanism of action. Methods: The TCMSP database was used to screen the main active ingredients of Sanqi( Panax notoginseng),and the SEA database was used to predict the potential targets of the above components. The hepatocellular carcinoma-related targets were obtained from the Human Genome Annotation( Genecards)database. The Venn software was used to intersect the two. Obtain the target of Sanqi treatment of hepatocellular carcinoma. Cytoscape 3. 7. 1 software was used to construct the active ingredient-target network. The R language software package cluster Profiler was used to perform gene ontology( GO) and metabolic pathway( KEGG) enrichment analysis on the above targets. Combined with BioGrid,In Web_IM,and Omni Path databases to construct target protein interaction( PPI),Cytoscape software was used for visualization and network topology analysis to obtain core targets. SYBYL-X2 software was used for molecular docking of core targets and corresponding active ingredients to verify the binding strength. Results: A total of 7 main active ingredients including quercetin,β-sitosterol,stigmasterol,and ginsenoside rh2 were obtained,which could act on 32 targets related to hepatocellular carcinoma;these targets were significantly enriched in nuclear receptor activity. Transcription factor activity,direct ligand regulation sequence-specific DNA binding,steroid hormone receptor activity,proteoglycans in cancer,resistance to EGFR tyrosine kinase inhibitors and many other GO and KEGG entries. Conclusion: The effect of Sanqi( Panax notoginseng) in treating hepatocellular carcinoma reflects the characteristics of multiple components,multiple targets,and multiple pathways of traditional Chinese medicine,which provides a certain scientific basis for the screening and in-depth study of the effective components of Panax notoginseng.
作者
安景铄
孙文静
王樱博
陆地
AN Jingshuo;SUN Wenjing;WANG Yingbo;LU Di(Kunming Medical University,Kunming Yunnan China 650500)
出处
《中医学报》
CAS
2020年第4期848-852,共5页
Acta Chinese Medicine
基金
国家自然科学基金项目(31760292)。
关键词
三七
肝细胞癌
网络药理学
靶点
基因本体论
富集分析
药物作用机制
Sanqi(Panax notoginseng)
hepatocellular carcinoma
network pharmacology
target
gene ontology
enrichment analysis
action mechanism of medicine
