基于网络药理学和分子对接及动力学模拟探究何首乌治疗乳腺癌的分子机制  

Based on the network pharmacology,molecular docking and dynamics simulation to explore the molecular mechanism of Polygonum multiflorum Thunb in the treatment of breast cancer

作　　者：胡蝶 周俊杰 盛锐 高朝政 李雪雅 李平[2] HU Die;ZHOU Junjie;SHENG Rui;GAO Chaozheng;LI Xueya;LI Ping(Graduate School,Anhui University of Chinese Medicine,Hefei Province,Anhui 230012,China;Department of Integrated Chinese and Western Medicine in Oncology,the First Affiliated Hospital of Anhui Medical University,Anhui Province,Hefei 230022,China)

机构地区：[1]安徽中医药大学研究生院,安徽合肥230012 [2]安徽医科大学第一附属医院中西医结合肿瘤科,安徽合肥230022

出　　处：《中国当代医药》2025年第11期9-15,共7页China Modern Medicine

基　　金：安徽省高校科研项目(2022AH051162)。

摘　　要：目的利用网络药理学与分子对接技术,探讨何首乌治疗乳腺癌的活性成分、靶点及其作用机制。方法基于中药系统药理学数据库与分析平台和中国知网数据库收集何首乌的活性成分和靶点,通过Gene Cards、基因组数据库和在线人类孟德尔遗传数据库筛选乳腺癌相关基因,并与何首乌靶基因取交集。利用String数据库分析交集基因,构建蛋白质相互作用(PPI)网络,并采用Cytoscape 3.7.2软件分析PPI网络的聚类模块,筛选出核心靶基因,构建药物-活性成分-靶点网络图。使用Metascape数据库和Hip lot在线工具进行基因本体论(GO)富集和基因组百科全书(KEGG)通路分析;通过CB-Dock2平台进行分子对接,使用Gromacs v2022.03软件对分子对接所得的蛋白-小分子复合物进行100 ns的分子动力学模拟。结果筛选预测出何首乌治疗乳腺癌的活性成分共28个,相关基因有304个。其主要通过调控丝氨酸/苏氨酸蛋白激酶(AKT1)、信号转导与转录激活因子3(STAT3)、缺氧诱导因子1α(HIF1A)、信号转导与转录激活因子1(STAT1)、酪氨酸激酶(SRC)和B细胞淋巴瘤2(BCL2)等关键癌症相关基因,以及PI3K-Akt、MAPK、内分泌抗性等信号通路发挥治疗作用,分子对接结果显示,何首乌与关键靶点均具有较好结合活性。结论通过分子对接和网络药理学分析,证实何首乌治疗乳腺癌具有多成分、多靶点、多途径的特点。未来研究可重点关注AKT1、STAT3、HIF1A、STAT1、SRC和BCL2等靶点及其相关信号通路,为中药单体药物研发、分子生物学实验及相关临床研究提供理论依据。Objective To explore the active components,targets and mechanisms of Polygonum multiflorum Thunb in the treatment of breast cancer using network pharmacology and molecular docking technology.Methods The active components and targets of Polygonum multiflorum Thunb were collected based on the pharmacology database and analysis platform of traditional Chinese medicine systems pharmacology and China national knowledge infrastructure.Breast cancer related genes were screened through Gene Cards,genome database and online mendelian inheritance in man,and the intersection of Polygonum multiflorum Thunb target genes was selected.The intersection genes were analyzed using String database to construct the protein-protein interaction(PPI)network,and Cytoscape 3.7.2 software was adopted to analyze the clustering module of PPI network,screen out the core target genes,and construct the drug-active ingredient-target network diagram.Genetic ontological(GO)and kyoto encyclopedia of genes and genomes(KEGG)pathway were analyzed using Metascape database and Hip lot online tool.Molecular docking was carried out on the CB-Dock2 platform,and Gromacs v 2022.03 software was used to simulate 100 ns molecular dynamics of the protein-small molecule complex obtained by molecular docking.Results A total of 28 active ingredients and 304 genes related to the treatment of breast cancer were predicted by screening.It was mainly function regulated by AKT serine/threonine kinase 1(AKT1),signal transducer and activator of transcription 3(STAT3),hypoxia-inducible factor 1α(HIF1A),signal transducer and activator of transcription 1(STAT1),src tyrosine kinase(Src)and B-cell lymphoma 2(BCL2).The signaling pathways of PI3K-Akt,MAPK,and endocrine resistance played therapeutic roles.Molecular docking results showed that Polygonum multiflorum Thunb had good binding activity to key targets.Conclusion Through molecular docking and network pharmacological analysis,it was confirmed that Polygonum multiflorum Thunb has the characteristics of multi-component,multi

关 键 词：何首乌 乳腺癌 网络药理学 分子对接 分子动力学 

分 类 号：R737.9[医药卫生—肿瘤]