基于网络药理学探讨 治疗卵巢癌的作用机制及木犀草素对 PI3K/AKT 通路的影响。
Exploring the Mechanism of against Ovarian Cancer based on Network Pharmacology and the Influence of Luteolin on the PI3K/AKT Pathway.
机构信息
Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.
出版信息
Comb Chem High Throughput Screen. 2024;27(1):157-167. doi: 10.2174/1386207326666230627114111.
BACKGROUND
Ovarian cancer (OC) is a commonly diagnosed female cancer around the world. The Chinese herbal medicine has an anti-cancer effect. However, there is no relevant report on whether is effective in treating OC, and the corresponding mechanism is also unknown.
OBJECTIVE
This study was projected to excavate the active components and underpinned molecular mechanisms of in treating ovarian cancer (OC) through network pharmacology combined with in vitro experiments.
METHODS
The essential active components of were selected using the TCMSP database. The OC-related targets were selected by GeneCards, intersecting targets were obtained by Venn Diagram. The core targets were obtained through the PPI network and Cytoscape, and the key pathway was gained through GO and KEGG enrichment analyses. Meanwhile, docking conformation was observed as reflected by molecular docking. MTT, colony formation assay and flow cytometer (FCM) analysis were performed to determine cell proliferation and apoptosis, respectively. Finally, Levels of various signaling proteins were evaluated by western blotting.
RESULTS
Luteolin, β-sitosterol and their corresponding targets were selected as the essential active components of . 76 intersecting targets were obtained by Venn Diagram. TP53, AKT1, and TNF were obtained through the PPI network and Cytoscape, and the key pathway PI3K/AKT was gained through GO and KEGG enrichment analyses. A good docking conformation was observed between luteolin and AKT1. Luteolin could hinder A2780 cell proliferation, induce cell apoptosis and enhance the inhibition of the PI3K/AKT pathway.
CONCLUSION
It was verified in vitro that luteolin could hinder OC cell proliferation and activate the PI3K/AKT pathway to lead to apoptosis.
背景
卵巢癌（OC）是一种在全球范围内常见的女性癌症。中药具有抗癌作用。然而，目前尚无关于 是否对 OC 有效及其相应机制的相关报道。
目的
本研究旨在通过网络药理学结合体外实验，挖掘 治疗卵巢癌（OC）的活性成分及潜在分子机制。
方法
采用 TCMSP 数据库筛选 的必需活性成分。通过 GeneCards 选择 OC 相关靶点，通过 Venn 图获得交集靶点。通过 PPI 网络和 Cytoscape 获得核心靶点，通过 GO 和 KEGG 富集分析获得关键通路。同时，通过分子对接观察对接构象。采用 MTT、集落形成实验和流式细胞术（FCM）分析分别检测细胞增殖和细胞凋亡。最后，通过 Western blot 评估各种信号蛋白的水平。
结果
从 中筛选出木犀草素、β-谷甾醇及其相应的靶点作为 的必需活性成分。通过 Venn 图获得 76 个交集靶点。通过 PPI 网络和 Cytoscape 获得 TP53、AKT1 和 TNF 核心靶点，通过 GO 和 KEGG 富集分析获得关键通路 PI3K/AKT。木犀草素与 AKT1 之间观察到良好的对接构象。木犀草素可抑制 A2780 细胞增殖，诱导细胞凋亡，并增强对 PI3K/AKT 通路的抑制作用。
结论
体外实验验证了木犀草素可抑制 OC 细胞增殖，激活 PI3K/AKT 通路，诱导细胞凋亡。
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