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目的 基于网络药理学筛选参芪扶正方治疗胃癌的核心靶基因，并分析其可能的作用机制。方法 通过TCMSP数据库获取参芪扶正方各活性成分对应的蛋白靶基因信息，通过GeneCards和OMIM数据库检索获得胃癌相关靶基因，并与参芪扶正方靶基因取交集，筛选获得参芪扶正方与胃癌之间的共同作用靶基因。将参芪扶正方与胃癌之间的共同作用靶基因导入STRING在线平台，构建PPI网络图，筛选得到参芪扶正方治疗胃癌的核心靶基因。通过Cytoscape 3.7.2软件，构建参芪扶正方中每味中药与胃癌的交集靶点图，通过拓扑分析筛选出参芪扶正方治疗胃癌的核心有效活性成分。借助DAVID在线平台对参芪扶正方-胃癌共同作用靶基因进行基因本体（GO）功能分析及京都基因与基因组百科全书（KEGG）通路富集分析。采用分子对接技术观察核心有效活性成分与核心靶点蛋白的分子结合能。结果 共获得参芪扶正方靶基因234个，胃癌相关靶基因2 172个，取交集后得到靶基因135个。筛选得到参芪扶正方治疗胃癌的核心靶基因为蛋白激酶B(AKT)、哺乳动物雷帕霉素靶蛋白（mTOR），参芪扶正方的核心有效活性成分为芹菜素、大豆黄素。GO功能及KEEG富集分析结果显示，参芪扶正方治疗胃癌的靶基因在调控细胞凋亡、基因表达等方面可能起到关键作用，涉及的主要通路为脂质与动脉粥样硬化以及PI3K/AKT信号通路。分子对接结果显示，参芪扶正方核心有效活性成分与核心靶点蛋白间均具有良好的结合效能。结论 参芪扶正方治疗胃癌的核心靶基因为AKT、mTOR，其机制与调控PI3K/AKT/mTOR信号通路有关。
Abstract：Objective To identify the core target genes and to investigate the potential mechanisms of Shenqi Fuzheng formula(SQFZ) in the treatment of gastric cancer(GC) using network pharmacology. Methods The active ingredient targets of the SQFZ were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). GC-related genes were collected from the GeneCards and OMIM databases. Common targets between SQFZ target genes and GC-related genes were identified as potential therapeutic targets. A protein-protein interaction(PPI) network was constructed using the STRING database, and core targets were identified through topological analysis. We used the Cytoscape 3. 7. 2 software to construct the intersection target map of each Chinese medicinal herb in the SQFZ and the gastric cancer, and through topological analysis, we identified the core effective active ingredients of the SQFZ for the treatment of gastric cancer. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed using the DAVID database. Finally, molecular docking was carried out to evaluate the binding affinity between the core bioactive compounds and the core target proteins. Results A total of 234 potential targets of SQFZ and 2,172 GC-related targets were collected. The intersection of these datasets yielded 135 common targets. Topological analysis identified protein kinase B(AKT1) and mammalian target of rapamycin(mTOR) as the core therapeutic targets, with apigenin and daidzein determined to be the core bioactive ingredients of SQFZ. GO and KEGG analyses indicated that SQFZ primarily modulated apoptosis and gene expression, with significant involvement in the PI3K-AKT signaling pathway and "lipid and atherosclerosis". Molecular docking confirmed strong binding affinities between the core ingredients and target proteins. Conclusion This study suggests that AKT1 and mTOR are the core targets of SQFZ in GC treatment, and its therapeutic mechanism is closely associated with regulation of the PI3K/AKT/mTOR signaling pathway.
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基本信息:
DOI：
中图分类号:R273
引用信息:
[1]韩甜甜,石永泉,滕悦伶,等.参芪扶正方治疗胃癌的核心靶基因筛选及其机制分析[J].山东医药,2025,65(10):19-22+39.
基金信息:
山东省中医药科技项目（M-2022192）