基于网络药理学探讨益金方治疗肺癌的作用机制

Mechanism of Yijin Formula in the Treatment of Lung Cancer Based on Network Pharmacology

目的:基于前期研究成果并结合网络药理学及分子对接技术,探讨益金方治疗肺癌的作用机制。方法:从多个开放数据平台获取益金方药物作用基因和肺癌相关基因。基于Cytoscape探索药物成分-靶点关系谱,探寻关键化合物。基于STRING平台完成蛋白质-蛋白质相互作用(PPI)网络的建立,采用Cytoscape-CytoNCA拓扑分析筛选核心靶点。通过R-ClusterProfiler对靶点进行基因本体(GO)和京都基因与基因组百科全书富集分析。最后,利用AutoDock对关键有效成分与肺癌通路相关核心靶点进行对接验证。结果:益金方的主要药物有效成分有157个,其包含潜在治疗靶点235个。通过5个数据平台共获得了8585个肺癌相关靶点。药物潜在治疗靶点和数据平台的共享靶点为215个。从PPI核心网络中筛选核心靶点18个。GO功能富集分析结果显示,相关靶点在各种生物过程、细胞功能方面富集显著,靶点与肺癌信号通路关系密切。根据分子对接结果,紫杉叶素、槲皮素、柚皮素、木犀草素、甘草查尔酮A、山柰酚、异鼠李素、薯蓣皂苷元和刺槐素能够与肺癌通路相关的核心靶点紧密结合。结论:益金方的主要药物有效成分可能通过多个靶点和信号通路干预肺癌,这可能是该方产生治疗效果的机制之一。

OBJECTIVE:To probe into the mechanism of Yijin formula in the treatment of lung cancer based on previous research results,network pharmacology and molecular docking technology.METHODS:Yijin formula drug-acting genes and lung cancer-related genes were obtained from multiple open data platforms.Drug component-target correlation and key compounds were explored based on Cytoscape.Protein-protein interaction(PPI)network was established based on STRING platform,and Cytoscape-CytoNCA topological analysis was used to screen the core targets.Gene ontology(GO)and Kyoto gene and genome encyclopedia analysis of targets were performed by R-ClusterProfiler.Finally,AutoDock was used to validate the docking of key active components with core targets related to lung cancer pathways.RESULTS:The active components of Yijin formula were 157,which contained 235 potential therapeutic targets.A total of 8585 lung cancer-related targets were obtained from 5 data platforms.The number of potential therapeutic targets shared by the drug and the data platforms was 215.A total of 18 core targets were screened from the PPI core network.GO functional enrichment analysis showed that the related targets were significantly enriched in various biological processes and cell functions,and the targets were closely related to lung cancer signaling pathways.According to molecular docking results,paclitaxel,quercetin,naringenin,lignocerotoxin,glycyrrhizin chalcone A,kaempferol,isorhamnetin,diosgenin element and aconitine were able to bind tightly to the core targets associated with the lung cancer pathway.CONCLUSIONS:The active components of Yijin formula may intervene in lung cancer through multiple targets and signaling pathways,which may be one of the mechanisms of therapeutic effects.