基于网络药理学和分子对接的白藜芦醇治疗口腔鳞状细胞癌的机制研究  

Network pharmacology and molecular docking reveal the mechanism of resveratrol in oral squamous cell carcinoma treatment

作　　者：陈虹君 雷奇 王治林 钟晓武[3] 邱亚[4] 李丽华[1] CHEN Hongjun;LEI Qi;WANG Zhilin;ZHONG Xiaowu;QIU Ya;LI Lihua(Department of Stomatology,Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,China;Department of Stomatology,North Sichuan Medical College,Nanchong 637000,China;Clinical Laboratory Department of Affiliated Hospital of Chuanbei Medical College,Nanchong 637000,China;Medical Research Center of Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,China)

机构地区：[1]川北医学院附属医院口腔科,四川南充637000 [2]川北医学院口腔医学系,四川南充637000 [3]川北医学院附属医院检验科,四川南充637000 [4]川北医学院附属医院医学研究中心,四川南充637000

出　　处：《口腔疾病防治》2024年第3期178-187,共10页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：南充市应用技术研究与开发专项项目(20YFZJ0090);川北医学院大学生创新创业计划项目(S202210634077,S202310634075)。

摘　　要：目的通过网络药理学及分子对接等生物学信息方法,探讨白藜芦醇治疗口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)的分子机制,为白藜芦醇治疗OSCC的临床应用提供参考。方法利用Swiss Target Prediction(http://www.swisstargetprediction.ch)、SEA数据库(http://sea.bkslab.org)、Pharm mapper数据库(http://lilab-ecust.cn)检索获得白藜芦醇的相关靶点,以DISGENET(www.disgenet.org)、OMIM(https://omim.org)、GeneCards(https://www.genecards.org)数据库筛选OSCC疾病靶点,取药物与疾病靶点的交集,再采用Cytoscape 3.7.2软件构建“药物-疾病-靶点-通路”网络,String数据库构建靶蛋白相互作用网络,采用DAVID数据库对关键蛋白进行富集分析,最后通过AutoDock及PyMOL对关键蛋白进行分子对接验证,结合富集分析和分子对接结果预测白藜芦醇治疗OSCC可能的分子作用机制;细胞水平采用Western blot检测不同浓度(50、100μmol/L)白藜芦醇对OSCC细胞株HSC-3细胞Src酪氨酸激酶(Src tyro-sine kinase,SRC)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、雌激素受体基因1(estrogen receptor gene 1,ESR1)及磷脂酰肌醇三激酶/蛋白激酶B(phosphatidylinositol 3 kinase/protein kinase B,PI3K/AKT)信号通路蛋白表达的影响。结果数据库得到白藜芦醇药物靶点243个,OSCC疾病靶点6094个,将药物与疾病的靶点进行交集获得116个潜在靶点,潜在靶点主要集中参与体内蛋白质自磷酸化、肽基酪氨酸磷酸化、跨膜受体蛋白酪氨酸激酶信号通路、RNA聚合酶Ⅱ启动子转录的正调控等生物过程,干预PI3K/AKT信号通路发挥抗OSCC的作用。分子对接结果表明白藜芦醇与EGFR、ESR1、SRC等OSCC关键靶点具有较好的结合活性。细胞实验结果表明,白藜芦醇药物干预以剂量依赖的方式抑制了HSC-3细胞中SRC、EGFR、ESR1及p-PI3K和p-AKT的蛋白表达。结论白藜芦醇对OSCC细胞SRC、EGFR、ESR1、p-PI3K、p-AKT靶点具有抑制作用�Objective To explore the molecular mechanism of resveratrol(RES)in the treatment of oral squamous cell carcinoma(OSCC)through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.Methods The Swiss Target Prediction(http://www.swisstargetprediction.ch),SEA(http://sea.bkslab.org)database,and Pharm mapper database(http://lilab-ecust.cn)were used to retrieve RES-related targets,and the DISGENET(www.disgenet.org),OMIM(https://omim.org)and GeneCards(https://www.genecards.org)databases were used to screen OSCC disease targets.The intersection of drugs and disease targets was determined,and Cytoscape 3.7.2 software was used to construct a"drug-diseasetarget pathway"network.The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database was used to construct a target protein interaction network,and the DAVID database was used for enrichment analysis of key proteins.Finally,molecular docking validation of key proteins was performed using AutoDock and PyMOL.The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC;western blot was used to determine the effect of resveratrol at different concentrations(50,100)μmol/L on the expression of Src tyrosine kinase(SRC),epidermal growth factor receptor(EGFR),estrogen receptor gene 1(ESR1),and phosphatidylinositol 3 kinase/protein kinase B(PI3K/AKT)signaling pathway proteins in OSCC HSC-3 cells.Results A total of 243 targets of RES drugs and 6094 targets of OSCC were identified.A total of 116 potential common targets were obtained by intersecting drugs with disease targets.These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation,peptide tyrosine phosphorylation,transmembrane receptor protein tyrosine kinase signaling pathway,and positive regulation of RNA polymerase Ⅱ promoter transcription,and

关 键 词：白藜芦醇 口腔鳞状细胞癌 网络药理学 分子对接 SRC酪氨酸激酶 表皮生长因子受体 雌激素受体基因1 磷脂酰肌醇三激酶/蛋白激酶B信号通路 

分 类 号：R78[医药卫生—口腔医学]