Department of Pharmacology, College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, 050200 Hebei Province, China.
Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000 Hebei Province, China.
Dis Markers. 2021 Jun 29;2021:4304507. doi: 10.1155/2021/4304507. eCollection 2021.
This study was aimed at exploring the regulatory mechanism of Xiaoyao San (XYS) and its main compound, Stigmasterol, in the biological network and signaling pathway of ovarian cancer (OC) through network pharmacology-based analyses and experimental validation.
The active compounds and targets of XYS were studied by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The GeneCards and OMIM databases were used to screen common targets of XYS in the treatment of OC. Combined with the STRING database and Cytoscape 3.6.0, the core compounds and targets of XYS were obtained. GO and KEGG pathway enrichment analyses of core target genes were carried out by using the Metascape and DAVID databases. Molecular docking has been achieved by using the AutoDock Vina program to discuss the interaction of the core targets and compounds of XYS in the treatment of OC. The effect of Stigmasterol on proliferation and migration were assessed by CCK8 and wound healing assay. Western blot and qRT-PCR were used to analyze the protein and mRNA expressions of PI3K, Akt, and PTEN after treatment of Stigmasterol.
A total of 113 common targets of XYS for the treatment of OC were obtained from 975 targets related to OC and 239 targets of XYS's effect. The main compounds of XYS include Quercetin, Naringenin, Isorhamnetin, and Stigmasterol, which mainly regulate the targets such as TP53, Akt1, and MYC and PI3K/Akt, p53, and cell cycle signal pathways. At the same time, molecular docking showed that Stigmasterol and Akt1 had good docking conformation. Stigmasterol inhibited OC cell proliferation and migration in vitro and reduced the protein and mRNA expressions of the PI3K/Akt signaling pathway.
Stigmasterol as the one of the main compounds of XYS suppresses OC cell activities through the PI3K-Akt signaling pathway.
本研究旨在通过网络药理学分析和实验验证，探讨逍遥散（XYS）及其主要化合物豆甾醇在卵巢癌（OC）生物网络和信号通路中的调控机制。
采用中药系统药理学数据库和分析平台（TCMSP）研究 XYS 的活性化合物和靶标。利用 GeneCards 和 OMIM 数据库筛选 XYS 治疗 OC 的共同靶标。结合 STRING 数据库和 Cytoscape 3.6.0 获得 XYS 的核心化合物和靶标。利用 Metascape 和 DAVID 数据库对核心靶基因进行 GO 和 KEGG 通路富集分析。采用 AutoDock Vina 程序进行分子对接，探讨 XYS 治疗 OC 的核心靶标和化合物的相互作用。采用 CCK8 和划痕愈合实验评估豆甾醇对增殖和迁移的影响。采用 Western blot 和 qRT-PCR 分析豆甾醇处理后 PI3K、Akt 和 PTEN 的蛋白和 mRNA 表达。
从与 OC 相关的 975 个靶标和 XYS 的 239 个作用靶标中，共获得 XYS 治疗 OC 的 113 个共同靶标。XYS 的主要化合物包括槲皮素、柚皮素、异鼠李素和豆甾醇，主要调节 TP53、Akt1、MYC 和 PI3K/Akt、p53、细胞周期信号通路等靶标。同时，分子对接表明豆甾醇和 Akt1 具有良好的对接构象。豆甾醇在体外抑制 OC 细胞增殖和迁移，并降低 PI3K/Akt 信号通路的蛋白和 mRNA 表达。
豆甾醇作为 XYS 的主要化合物之一，通过 PI3K-Akt 信号通路抑制 OC 细胞活性。
