基于网络药理学和分子对接技术阐释芪甲扶正方治疗肺腺癌相关性疲乏的潜在作用机制

Potential Action Mechanism of Qijia Fuzheng Formula in the Treatment of Cancer Related Fatigue of Lung Adenocarcinoma Based on Network Pharmacology and Molecular Docking

目的:探究芪甲扶正方治疗肺腺癌相关性疲乏的作用机制。方法:基于中药系统药理学数据库与分析平台(TCMSP)、中医药综合数据库(TCMID)、Pubchem、Swiss Target Prediction等数据库收集芪甲扶正方有效成分及作用靶点;通过GeneCards、OMIM等数据库获取“肺腺癌相关性疲乏”相关靶基因;将药物靶点映射到疾病靶点集合上,获取交集基因;使用String构建蛋白质-蛋白质相互作用(PPI)网络;通过Cytoscape构建药物-成分-靶点调控网络;利用DAVID数据库对芪甲扶正方治疗肺腺癌相关性疲乏的靶点进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析;运用Genebank数据库分析交集基因的组织器官定位;利用AutoDock Vina_1.1.2分析主要活性成分和关键靶点的结合能力,并使用PYMOL软件将对接结果进行可视化展示。结果:调控网络共包含9味中药、108种活性成分、87个靶基因;和CASP3、VEGFA、EGFR、MYC、IL-6;KEGG富集分析涉及PI3K-AKT、p53、TNF、MAPK、ErbB、Ras、FoxO等通路;关键基因主要分布在肺、红细胞、T细胞、B细胞;分子对接结果表明EGFR与木犀草素、IL-6、MAKP3与β-谷甾醇、MAKP8与鞣花酸具有较强的结合能力。结论:芪甲扶正方活性成分鞣花酸、β-谷甾醇等,可能通过作用于EGFR、IL-6、MAKP3、MAKP8等靶点,进而通过调节PI3K-AKT通路发挥对肺腺癌相关性疲乏的治疗作用。

Objective:To explore the action mechanism of Qijia Fuzheng Formula in the treatment of fatigue-related lung adenocarcinoma.Methods:Based on databases such as TCMSP,TCMID,Pubchem,Swiss Target Prediction,etc.,the active ingredients and targets of Qijia Fuzheng Formula were collected;relevant target genes of“pulmonary adenocarcinoma-related fatigue”from databases such as GeneCards and OMIM were obtained;drug targets were mapped to diseases target set.The intersection genes on the target set were obtained;String was used to construct a protein-protein interaction(PPI)network;Cytoscape was used to construct a drug-component-target regulatory network;DAVID database was used to enrich(GO,KEGG)analysis of the targets of Qijiafuzheng Formula in the treatment of lung adenocarcinoma-related fatigue;Genebank database was used to analyze the tissue and organ location of intersection genes;AutoDock Vina_1.1.2 was used to analyze the main active ingredients and key binding ability of the target,and PYMOL was used software to visualize the docking results.Results:The drug-compound-target network consisted of 9 drugs,108 compounds and 87 targets;and CASP3,VEGFA,EGFR,MYC,IL-6;KEGG enrichment analysis involved PI3K-AKT,p53,TNF,MAPK,ErbB,Ras,FoxO and other pathways;key genes were mainly distributed in lungs,red blood cells,T cells,B cells;molecular docking results showed that EGFR and luteolin,IL-6,MAKP3 andβ-sitosterol,MAKP8 and ellagic acid had strong binding ability.Conclusion:The active ingredients of Qijia Fuzheng Formula,such as ellagic acid andβ-sitosterol,may act on EGFR,IL-6,MAKP3,MAKP8 and other targets,and then play a role in the treatment of lung adenocarcinoma-related fatigue by regulating the PI3K-AKT pathway effect.