基于网络药理学和分子对接研究紫藤瘤对胃癌的作用机制及初步验证  

Study on anti-gastric cancer mechanism of Wisteria sinensis tumor based on network pharmacology,molecular docking technology and experimental verification

作　　者：杨辉[1] 王文君 徐泽荣 黄宇飞 程卉[3] 刘劲松 王国凯 YANG Hui;WANG Wen-jun;XU Ze-rong;HUANG Yu-fei;CHENG Hui;LIU Jin-song;WANG Guo-kai(The First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,China;School of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012,China;Experimental Research Center,Anhui University of Chinese Medicine,Hefei 230038,China;Anhui Province Key Laboratory of Research&Development of Chinese Medicine,Hefei 230012,China;Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application,Hefei 230012,China)

机构地区：[1]安徽中医药大学第一附属医院,安徽合肥230031 [2]安徽中医药大学药学院,安徽合肥230012 [3]安徽中医药大学科研技术中心,安徽合肥230038 [4]中药研究与开发安徽省重点实验室,安徽合肥230012 [5]药物制剂技术与应用安徽省重点实验室,安徽合肥230012

出　　处：《中国药理学通报》2022年第11期1739-1747,共9页Chinese Pharmacological Bulletin

基　　金：安徽省自然科学基金资助项目(No.1308085QH154);国家重点专科(中医外科)开放性课题项目(No.2016zkkf005);安徽省高校优秀青年人才支持计划重点项目(No.gxyqZD2019035)。

摘　　要：目的基于网络药理学和分子对接技术探讨紫藤瘤对胃癌的作用机制,并通过实验进行验证。方法通过数据库筛选紫藤瘤活性成分及对应靶点,同时收集疾病靶点,利用Venny2.1.0平台获取疾病和药物靶点的交集。使用String数据库对共有靶点进行靶蛋白相互作用(PPI)网络构建、使用Metascape数据库对靶点进行基因本体(GO)富集分析及京都基因与基因组百科全书(KEGG)通路分析,通过Cytoscape3.7.2软件构建“成分-靶点-通路”交互网络分析。利用Autodock Vina软件将关键靶点与相应的活性成分进行分子对接;利用体外细胞实验验证。结果筛选出8个活性成分、308个药物靶点和269个疾病靶点,19个交集靶点,KEGG通路富集分析出7条通路。分子对接结果显示紫藤瘤活性成分能够和胃癌关键靶点产生较稳定的结合。体外结果表明,紫藤瘤中芒柄花素对胃癌细胞具有一定的活性,且诱导胃癌SGC-7901细胞凋亡,增加了胞内钙离子的水平。结论揭示了紫藤瘤治疗胃癌的潜在成分及其调控网络,明确了紫藤瘤中芒柄花素的抗肿瘤作用,且可能与诱导胃癌SGC-7901细胞凋亡有关。Aim To investigate the pharmacological mechanism of Wisteria sinensis tumor in the treatment of gastric cancer,using a network pharmacology and molecular docking approach,with verification of the results by experiments.Methods The main active components and corresponding targets of Wisteria sinensis tumor monocytogenes,as well as the disease targets of gastric cancer,were obtained through the network pharmacology database.The Venny 2.1.0 platform was used to take the intersection of drug and disease.The String database was used to construct target protein interaction(PPI)network for common targets,and Metascape database was used to analyze GO function enrichment KEGG pathway enrichment of related targets.The interactive network of“component-target-pathway”of Wisteria sinensis tumor on gastric cancer was constructed by Cytoscape3.7.2 software.The molecular docking of the key targets and active compunds was carried out by using Autodock Vina software.The effect of Wisteria sinensis tumor on gastric cancer was verified by in vitro cell tests.Results A total of 8 main active components,290 drug targets and 251 gastric cancer-related targets were screened out.A total of 19 targets intersected between with drug and diseases.Seven pathways were involved in the treatment of gastric cancer by Wisteria sinensis tumor.The results of molecular docking showed that the main active components of Wisteria sinensis tumor had good binding ability with the key targets of gastric cancer.The results of in vitro experiments confirmed that,the formononetin from Wisteria sinensis tumor had certain activity on gastric cancer cells,and the formononetin could also induce apoptosis of gastric cancer SGC-7901 cells and increase the level of intracellular calcium ion.Conclusions This study preliminarily reveals the potential components and regulatory network of Wisteria sinensis tumor monocytogenes acting on gastric cancer clarified that Wisteria sinensis tumor monocytogenes has antitumor effect,and may be related to inducing apoptosis of

关 键 词：紫藤瘤 胃癌 网络药理学 分子对接 体外细胞实验 作用机制 

分 类 号：R284.1[医药卫生—中药学] R329.25[医药卫生—中医学] R319R735.2