基于网络药理学探析化痰消瘀方治疗食管癌的机制

Mechanism of the Huatan Xiaoyu prescription for esophageal cancer based on network pharmacology

目的:利用网络药理学方法来评估化痰消瘀方治疗食管癌机制和潜在目标靶点。方法:化痰消瘀方有效成分从TCMSP及Swiss Target Prediction数据库中获取的。从GeneCards、DisGeNet和OMIM数据库下载与食管癌相关的目标基因。蛋白质-蛋白质相互作用网络是使用String数据库和Cytoscape构建的。最后,采用基因本体论(GO)和京都基因与基因组学百科全书(KEGG)对目标靶点进行基因和基因组富集分析。使用AutoDock Vina对活性成分和目标基因之间的关系进行建模。结果:在食管癌中相关的基因中,158个与化痰消瘀的靶点重叠,主要包括丝氨酸/苏氨酸蛋白激酶(Akt Serine/Threonine Kinase,AKT)1、白细胞介素(Interleukin,IL)-6、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、肿瘤蛋白P53(Tumor Protein P53,TP53)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)8、半胱氨酸蛋白酶(Caspase,CASP)3等。这些靶点中前20个相互作用的蛋白质通过KEGG及GO富集分析表明,共同靶点参与了多种生物学过程和途径,包括DNA合成调控、基因表达调控、RNA代谢调控,缺氧诱导因子(Hypoxia Inducible Factor,HIF)-1信号通路和肿瘤坏死因子(Tumor Necrosis Factor,TNF)信号通路等。分子对接分析表明,活性成分与靶标蛋白能较好的结合。结论:本研究为深入分析化痰消瘀方作用机制提供了理论基础,为临床应用和潜在的新药开发提供思路。

Objective:To evaluate the mechanism and potential target targets of the Huatan Xiaoyu prescription(化痰消瘀方)for the treatment of esophageal cancer based on network pharmacology.Methods:The active ingredients of the Huatan Xiaoyu prescription were obtained from TCMSP and Swiss Target Prediction databases.Target genes associated with esophageal cancer were downloaded from GeneCards,DisGeNet and OMIM databases.PPI network was constructed using String database and Cytoscape.Finally,gene and genome enrichment analysis of target targets was performed using GO and KEGG.The relationship between active ingredients and target genes was modeled using AutoDock Vina.Results:Among the genes associated in esophageal cancer,a total of 158 overlapped with the targets of phlegm reduction and elimination,mainly including AKT1,IL-6,VEGFA,TP53,MAPK8,and CASP3.The top 20 interacting proteins among these targets were analyzed by KEGG and GO enrichment analysis,indicating that the common targets were involved in various biological processes and pathways,including regulation of DNA synthesis,regulation of gene expression,regulation of RNA metabolism,HIF-1 signaling pathway and TNF signaling pathway.Molecular docking analysis showed that the active ingredients could bind well to the target proteins.Conclusion:This study provides a theoretical basis for an in-depth analysis of the mechanism of action of the phlegmeliminating formula,and provides ideas for practical clinical applications and potential new drug development.