基于网络药理学及分子对接探讨丁香-柿蒂治疗食管癌的分子机制

目的预测丁香-柿蒂药对治疗食管癌的作用机制。方法通过中药系统药理学分析平台(TCMSP)筛选出丁香、柿蒂的活性成分;在PubChem数据库中搜索活性成分的化学分子式,将化学分子式上传至靶点预测数据库(SwissTargetPrediction)得到预测的基因靶点。以"esophageal cancer"为关键词,在基因疾病关联数据库(DisGeNET)中检索食管癌的相关靶基因,将其与药对的活性成分靶基因相互映射,筛选出共同靶点。利用Cytoscape 3.7.1软件绘制活性成分-靶点网络。将筛选出来的靶点在蛋白质相互作用网络数据库(STRING)中构建蛋白互作网络;同时,选择生物信息分析学习平台(Omicshare)进行基因GO功能及KEGG通路的富集分析。使用分子对接软件(AutoDock Vina),将核心靶点与活性成分进行分子对接,并使用分子绘图软件(PyMol)和(LigPlus)绘制图片。结果从丁香-柿蒂药对中共筛选出11个活性成分,包括槲皮素(quercetin)、山奈酚(kaempferol)、齐墩果酸(oleanolic acid)等,主要作用于AKT1、SRC、EGFR 3个靶点,主要涉及FoxO、Relaxin、PI3K-AKT、Rap1等信号通路。结论本研究通过网络药理学的方法预测丁香-柿蒂药对治疗食管癌的分子机制,为丁香-柿蒂药对治疗食管癌的基础研究和临床应用提供参考。

The Active Mechanism of“Caryophylliti Flos-Kaki Calyx”on Esophageal Cancer Based on Network Pharmacology and Molecular Docking

Objective The study was designed to predict the mechanism of"Caryophylliti flos-Kaki calyx"on treating esophageal cancer based on network pharmacology.Methods The active components of"Caryophylliti flos-Kaki calyx"were searched by TCMSP.The chemical formulas of the active components were searched in PubChem and uploaded to SwissTargetPrediction database to obtain the predicted gene targets.Taking"esophageal cancer"as the keyword,the related target genes were retrieved from the DisGeNET database and mapped to the active ingredients of the drug pairs in order to screen common targets.Cytoscape 3.7.1 software was used to construct an active component-target network.The potential targets were mapped into protein-protein interaction network in STRING database.Meanwhile,enrichment analysis of GO function and KEGG pathway were performed by Omicshare platform.AutoDock Vina software was used to dock the core targets with the active ingredients,and PyMol and LigPlus software were used to draw pictures.Results Eleven active ingredients,including quercetin,kaempferol and oleanolic acid,were screened from Caryophylliti Flos-kaki Calyx.They mainly act on three targets:AKT1,SRC and EGFR.They play a role in the treatment of esophagus cancer by involving in different signal pathways such as FoxO,Relaxin,PI3 K-AKT and Rap1.Conclusion In this study,network pharmacology was used to predict the molecular mechanism of"Caryophylliti flos-Kaki calyx"in the treatment of esophagus cancer.The results reflect the characteristics of traditional Chinese medicine in treating diseases,and provide references for the clinical application in the treatment of esophagus cancer with"Caryophylliti flos-Kaki calyx".