口腔疾病防治Issue(3)：178-187,10.DOI:10.12016/j.issn.2096-1456.2024.03.003
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 car-cinoma treatment
摘要
Abstract
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 map-per 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 tar-gets.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)data-base was used to construct a target protein interaction network,and the DAVID database was used for enrichment analy-sis 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 re-ceptor 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 6 094 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,trans-membrane receptor protein tyrosine kinase signaling pathway,and positive regulation of RNA polymerase Ⅱ promot-er transcription,and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects.The docking results of resveratrol with OSCC molecules indicated that key targets,such as EGFR,ESR1,and SRC,have good binding activi-ty.The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC,EGFR,ESR1,p-PI3K,and p-AKT in HSC-3 cells in a dose-dependent manner.Conclusion RES can inhibit the expres-sion of its targets EGFR,ESR1,SRC,p-PI3K,and p-AKT in OSCC cells.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Key words
resveratrol/oral squamous cell carcinoma/network pharmacology/molecular docking/Src tyro-sine kinase/epidermal growth factor receptor/estrogen receptor gene 1/phosphatidylinositol 3 kinase/protein kinase B signaling pathway分类
医药卫生引用本文复制引用
陈虹君,雷奇,王治林,钟晓武,邱亚,李丽华..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[J].口腔疾病防治,2024,(3):178-187,10.基金项目
This study was supported by the grants from Nanchong Applied Technology Research and Development Project(No.20YFZJ0090) （No.20YFZJ0090）
Innovation and Entrepreneurship Program for College Students of North Sichuan Medical College(No.S202210634077,No.S202310634075).南充市应用技术研究与开发专项项目(20YFZJ0090) （No.S202210634077,No.S202310634075）
川北医学院大学生创新创业计划项目(S202210634077,S202310634075) （S202210634077,S202310634075）
