| 摘要: |
| 目的：利用网络药理学和生物信息学分析探讨参苓白术散治疗胃癌的作用机制。方法：依托中药系统药理学数据库与分析平台（Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP）建立特殊的筛选标准，收集、预测参苓白术散各药物的活性成分和作用靶点。从癌症基因组图谱（The Cancer Genome Atlas，TCGA）和基因表达综合数据库（Gene Expression Omnibus，GEO）获取胃癌主要作用靶点，通过分析计算出差异基因作为胃癌预测的疾病靶点，并通过GeneCards、在线人类孟德尔遗传（Online Mendelian Inheritance in Man，OMIM）和治疗靶点数据库（Therapeutic Target Database，TTD）检索疾病靶点作为补充。通过基因/蛋白质相互作用检索搜索工具(Search Tool for the Retrieval of Interacting Genes/Proteins，STRING)平台数据库进行蛋白质-蛋白质相互作用(protein-protein interatction，PPI)网络分析，运用 Cytoscape软件构建蛋白互作网络并筛选核心靶点。通过使用注释、可视化和综合发现（Database for Annotation，Visualization，and Integrated Discovery，DAVID）数据库对共同靶点进行基因本体(gene ontology，GO)功能注释与京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes，KEGG)通路富集分析，使用微生信在线生物信息学及可视化云平台进行可视化分析。采用AutoDock软件以及PyMOL构建分子对接模型并验证研究结果。结果：经筛选后得到参苓白术散活性成分190个及243个作用靶点，与胃癌交集靶点有176个，主要活性成分有槲皮素、山柰酚、叶黄素、豆甾醇、β-谷甾醇和柚皮素等，蛋白激酶B（protein kinase B，AKT）、肿瘤坏死因子（tumor necrosis factor，TNF）、肿瘤蛋白p53（tumor protein p53，TP53）、白细胞介素-6（interleukin-6，IL-6）、白细胞介素-1β（interleukin-1 Beta，IL-1β）和雌激素受体1（estrogen receptor 1，ESR1）等为关键基因。富集分析结果提示核心靶点主要作用于磷脂酰肌醇3-激酶（Phosphatidylinositol 3-kinase，PI3K）-AKT和丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）等多种免疫、炎症相关的信号通路，主要影响RNA聚合酶Ⅱ对转录的正向调节和基因表达的正调控等生物学过程。通过分子对接验证得到核心靶点与分子化合物的结合度良好。结论：参苓白术散可通过槲皮素、山柰酚、叶黄素等活性成分作用于AKT1、TNF、TP53等关键靶点，通过PI3K-AKT、MAPK等多种信号通路发挥抗胃癌的作用。 |
| 关键词: 参苓白术散 胃癌 生物信息学 分子对接 网络药理学 |
| DOI： |
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| Mechanism of action of Shenling Baizhu powder in treatment of gastric cancer：A study based on network pharmacology，bioinformatics，and molecular docking |
| SU Biqian,HU Yiting,ZHANG Qi’an |
| (Hunan University of Chinese Medicine，Changsha 410208，Hunan，China) |
| Abstract: |
| Objective：To investigate the mechanism of action of Shenling Baizhu powder in the treatment of gastric cancer based on network pharmacology and bioinformatics.Methods：Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to establish specific screening criteria.The active components of each drug in Shenling Baizhu powder were collected，and their action targets were predicted.The Cancer Genome Atlas and Gene Expression Omnibus were used to obtain the main action targets of gastric cancer，and differentially expressed genes were identified as the disease targets for predicting gastric cancer.GeneCards，Online Mendelian Inheritance in Man，and Therapeutic Target Database were searched for related disease targets as supplementation.The Search Tool for the Retrieval of Interacting Genes/Proteins database was used to perform a protein-protein interaction (PPI) network analysis，and Cytoscape software was used to construct a PPI network and identify core targets.The Database for Annotation，Visualization，and Integrated Discovery was used to perform gene ontology (GO) functional annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of common targets，and Weishengxin online bioinformatics analysis and visualization cloud platform were used for visual analysis.AutoDock software and PyMOL were used to construct a molecular docking model and verify research results.Results：A total of 190 active components and 243 action targets were obtained for Shenling Baizhu powder after screening，and there were 176 intersecting targets with gastric cancer.The main active components included quercetin，kaempferol，lutein，stigmasterol，beta-sitosterol，and naringenin，and the key genes included protein kinase B (AKT)，tumor necrosis factor (TNF)，tumor protein p53 (TP53)，interleukin-6，interleukin-1β，and estrogen receptor 1.The enrichment analysis showed that the core targets mainly acted on various signaling pathways associated with immunity and inflammation including the phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling pathway and the mitogen-activated protein kinase (MAPK) signaling pathway，mainly affecting the biological processes such as positive regulation of transcription by RNA polymerase Ⅱ and positive regulation of gene expression.Molecular docking showed good binding activity between the core targets and the molecular compounds.Conclusion：Shenling Baizhu powder acts on the key targets such as AKT1，TNF，and TP53 through multiple active components including quercetin，kaempferol，and lutein，and it exerts a therapeutic effect on gastric cancer through multiple signaling pathways including the PI3K-AKT signaling pathway and the MAPK signaling pathway. |
| Key words: Shenling Baizhu powder gastric cancer bioinformatics molecular docking network pharmacology |
