姚元谦;吕建林;柳琳琳;毛德文;黄娴;黄小英;

• 1:广西中医药大学
• 2:广西中医药大学第一附属医院

摘要(Abstract)：

目的 采用GEO基因芯片挖掘、网络药理学及分子对接技术分析解毒化瘀颗粒治疗肝癌的作用机制。方法 从GEO数据库下载肝癌的基因芯片数据集，利用R软件筛选出显著性差异基因，从TCMSP、SymMap、SwissTargetPrediction等数据库获取解毒化瘀颗粒的活性成分、药物靶点，运用Cytoscape软件及STRING、DAVID等平台，对药物-疾病交集靶点进行PPI、GO、KEGG分析，使用PyMOL、AutoDockTools1、AutoDock Vina等软件对活性成分-核心靶点进行分子对接验证。结果 得到肝癌显著性差异基因1 423个、解毒化瘀颗粒作用靶点682个，筛选出药物-疾病交集靶点122个。PPI拓扑分析得出的核心靶点有ESR1、PTGS2、CYP3A4、MMP9、AR、CYP1A1、PTPRC、TYMS、CDK1等。GO功能富集分析主要涉及氧化还原过程、环氧酶P450途径、细胞外泌体、ATP结合等，KEGG通路分析主要富集在化学致癌作用通路、细胞色素P450代谢通路、花生四烯酸代谢通路、P53信号通路、PI3K-Akt信号通路等。分子对接验证显示各主要活性成分与核心靶点间结合能<-5.0 kcal/mol。结论 解毒化瘀颗粒中的异鼠李素、β-谷甾醇、2-甲氧基-3-甲基-9,10-蒽醌、油酸乙酯、茵陈黄酮等活性成分，通过上调ESR1、CYP3A4、CYP1A1、PTPRC及下调PTGS2、MMP9、AR、TYMS、CDK1、PLK1等核心靶点，调控化学致癌作用通路、细胞色素P450代谢通路、花生四烯酸代谢通路、P53信号通路、PI3K-Akt信号通路等途径，从而抑制肝癌细胞的增殖、侵袭、扩散及对药物的耐药性。

关键词(KeyWords)： GEO芯片挖掘;网络药理学;分子对接;解毒化瘀颗粒;肝癌

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(81860839);; 广西自然科学基金项目(2020GXNSFAA238020);; 广西学位与研究生教育改革专项课题(JGY2015090);; 广西研究生教育创新计划资助项目(YCXJ2021059)

作者(Authors): 姚元谦;吕建林;柳琳琳;毛德文;黄娴;黄小英;

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