基于网络药理学探讨山柰酚治疗胃癌的作用机制。
Exploration in the Mechanism of Kaempferol for the Treatment of Gastric Cancer Based on Network Pharmacology.
机构信息
Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China.
Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, China.
出版信息
Biomed Res Int. 2020 Oct 21;2020:5891016. doi: 10.1155/2020/5891016. eCollection 2020.
BACKGROUND
Kaempferol is a natural polyphenol in lots of Chinese herbs, which has shown promising treatment for gastric cancer (GC). However, the molecular mechanisms of its action have not been systematically revealed yet. In this work, a network pharmacology approach was used to elucidate the potential mechanisms of kaempferol in the treatment of GC.
METHODS
The kaempferol was input into the PharmMapper and SwissTargetPrediction database to get its targets, and the targets of GC were obtained by retrieving the Online Mendelian Inheritance in Man (OMIM) database, MalaCards database, Therapeutic Target Database (TTD), and Coolgen database. The molecular docking was performed to assess the interactions between kaempferol and these targets. Next, the overlap targets of kaempferol and GC were identified for GO and KEGG enrichment analyses. Afterward, a protein-protein interaction (PPI) network was constructed to get the hub targets, and the expression and overall survival analysis of the hub target were investigated. Finally, the overall survival (OS) analysis of hub targets was performed using the Kaplan-Meier Plotter online tool.
RESULTS
A total of 990 genes related to GC and 10 overlapping genes were determined through matching the 24 potential targets of kaempferol with disease-associated genes. The result of molecular docking indicated that kaempferol can bind with these hub targets with good binding scores. These targets were further mapped to 140 GO biological process terms and 11 remarkable pathways. In the PPI network analysis, 3 key targets were identified, including ESR1, EGFR, and SRC. The mRNA and protein expression levels of EGFR and SRC were obviously higher in GC tissues. High expression of these targets was related to poor OS in GC patients.
CONCLUSIONS
This study provided a novel approach to reveal the therapeutic mechanisms of kaempferol on GC, which will ease the future clinical application of kaempferol in the treatment of GC.
背景
山奈酚是许多中草药中的一种天然多酚，已显示出对胃癌（GC）有治疗前景。然而，其作用机制尚未得到系统揭示。在这项工作中，采用网络药理学方法阐明山奈酚治疗 GC 的潜在机制。
方法
将山奈酚输入 PharmMapper 和 SwissTargetPrediction 数据库以获得其靶标，通过检索在线孟德尔遗传人类（OMIM）数据库、MalaCards 数据库、治疗靶标数据库（TTD）和 Coolgen 数据库获得 GC 的靶标。进行分子对接以评估山奈酚与这些靶标的相互作用。接下来，对山奈酚和 GC 的重叠靶标进行 GO 和 KEGG 富集分析。然后，构建蛋白质-蛋白质相互作用（PPI）网络以获得枢纽靶标，并对枢纽靶标的表达和总生存期进行分析。最后，使用 Kaplan-Meier Plotter 在线工具对枢纽靶标进行总生存期（OS）分析。
结果
通过将山奈酚的 24 个潜在靶标与疾病相关基因相匹配，确定了与 GC 相关的 990 个基因和 10 个重叠基因。分子对接结果表明，山奈酚可以与这些枢纽靶标良好结合。这些靶标进一步映射到 140 个 GO 生物过程术语和 11 个显著途径。在 PPI 网络分析中，确定了 3 个关键靶标，包括 ESR1、EGFR 和 SRC。GC 组织中 EGFR 和 SRC 的 mRNA 和蛋白表达水平明显升高。这些靶标的高表达与 GC 患者的不良 OS 相关。
结论
本研究为揭示山奈酚治疗 GC 的治疗机制提供了一种新方法，将有助于山奈酚在 GC 治疗中的临床应用。
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