基于网络药理学研究紫龙金片治疗口咽癌的作用机制

The Effect of Zilongjin Tablets in the Treatment of Oropharyngeal Cancer Based on Network Pharmacology

目的运用网络药理学与分子对接方法,从整体角度系统分析并预测紫龙金片治疗口咽癌的分子机制,为临床研究及新药研发提供参考。方法利用TCMSP数据库与YaTCM数据库获取紫龙金片中8种药物的主要活性成分及其相关靶点。检索GeneCards数据库获得口咽癌的作用靶点,并与活性成分的靶点取交集,获得紫龙金片治疗口咽癌的潜在作用靶点。在STRING数据库中获得各靶点的相互作用关系。利用Cytoscape 3.8.0软件构建紫龙金片-有效活性成分-潜在作用靶点网络及靶点的蛋白互作网络,筛选核心靶点。应用程序生成蛋白质-蛋白质相互作用(PPI)网络和“中药-活性成分-靶点”的可视化网络,并筛选出主要活性成分和核心靶点;运用David数据库对药物与疾病的共同基因进行GO和KEGG富集分析;利用AutoDuck 4.2.6进行核心靶点与主要成分的分子对接。结果通过网络构建分析发现,紫龙金片主要通过145个有效活性成分干预271个潜在靶点来治疗口咽癌,有效活性成分中以槲皮素、木犀草素和甾醇等成分为主,核心靶点为ALB、AKT1、TP53等。基因富集分析显示紫龙金片主要通过干预受体和通路活性以及调控PI3K-Akt、MAPK、IL-17、TNF、HIF-1等信号通路,发挥治疗口咽癌的作用。结论紫龙金片主要通过抑制肿瘤细胞增殖、诱导凋亡等发挥治疗口咽癌的作用。

Objective To systematically analyze and predict the molecular mechanism of Zilongjin Tablets in the treatment of oropharyngeal cancer from a holistic perspective by using network phar-macology and molecular docking methods,so as to provide reference for clinical research and new drug development.Methods The TCMSP database and YaTCM database were utilized to obtain the main active ingredients of the eight drugs in Zilongjin tablets and their related targets.The Gene-Cards database was searched to obtain the action targets of oropharyngeal cancer and the intersec-tion with the targets of the active ingredients was taken to obtain the potential action targets of Zi-longjin tablets for the treatment of oropharyngeal cancer.The interaction relationship of each target was obtained in STRING database.Cytoscape 3.8.0 software was used to construct the Zilongjin Tablet-active ingredient-potential action target network and protein-protein interaction network of the targets to screen the core targets.The program was used to generate a protein-protein interaction(PPI)network and a“TCM-active ingredient-target”visualisation network,and to screen the main active ingredients and core targets.GO and KEGG enrichment analyses of drug-disease common genes were performed using the David database.AutoDuck 4.2.6 was used to perform molecular docking between core targets and main ingredients.Results Through network construction analysis,Zilongjin Tablets were found to treat oropharyngeal cancer mainly through 124 active ingredients intervening in 271 potential targets,with quercetin,lignans and sterols as the main active ingredients,and ALB,AKT1,TP53 as the core targets.Gene enrichment analysis showed that Zilongjin Tablet mainly exerted its therapeutic effect on oropharyngeal cancer by interfering with the receptor and pathway activities as well as regulating the signalling pathways such as PI3K-Akt,MAPK,IL-17,TNF,HIF-1 and so on.Conclusion Zilongjin Tablets mainly play a role in the treatment of oropha-ryngeal cancer by inhibiting tumor cell proliferation and inducing apoptosis.