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基于网络药理学方法系统阐明槲皮素抗胃癌的作用机制。

Systematic Elucidation of the Mechanism of Quercetin against Gastric Cancer via Network Pharmacology Approach.

机构信息

Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.

出版信息

Biomed Res Int. 2020 Sep 3;2020:3860213. doi: 10.1155/2020/3860213. eCollection 2020.

Abstract

This study was aimed at elucidating the potential mechanisms of quercetin in the treatment of gastric cancer (GC). A network pharmacology approach was used to analyze the targets and pathways of quercetin in treating GC. The predicted targets of quercetin against GC were obtained through database mining, and the correlation of these targets with GC was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Next, the protein-protein interaction (PPI) network was constructed, and overall survival (OS) analysis of hub targets was performed using the Kaplan-Meier Plotter online tool. Finally, the mechanism was further analyzed via molecular docking of quercetin with the hub targets. Thirty-six quercetin-related genes were identified, 15 of which overlapped with GC-related targets. These targets were further mapped to 319 GO biological process terms and 10 remarkable pathways. In the PPI network analysis, six hub targets were identified, including AKT1, EGFR, SRC, IGF1R, PTK2, and KDR. The high expression of these targets was related to poor OS in GC patients. Molecular docking analysis confirmed that quercetin can bind to these hub targets. In conclusion, his study provided a novel approach to reveal the therapeutic mechanisms of quercetin on GC, which will ease the future clinical application of quercetin in the treatment of GC.

摘要

本研究旨在阐明槲皮素治疗胃癌(GC)的潜在机制。采用网络药理学方法分析槲皮素治疗 GC 的靶点和途径。通过数据库挖掘获得槲皮素治疗 GC 的预测靶点,并通过基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析分析这些靶点与 GC 的相关性。接下来,构建蛋白质-蛋白质相互作用(PPI)网络,并使用 Kaplan-Meier Plotter 在线工具对关键靶点进行总体生存(OS)分析。最后,通过槲皮素与关键靶点的分子对接进一步分析机制。鉴定出 36 个槲皮素相关基因,其中 15 个与 GC 相关靶点重叠。这些靶点进一步映射到 319 个 GO 生物学过程术语和 10 个显著途径。在 PPI 网络分析中,确定了 6 个关键靶点,包括 AKT1、EGFR、SRC、IGF1R、PTK2 和 KDR。这些靶点的高表达与 GC 患者的不良 OS 相关。分子对接分析证实槲皮素可以与这些关键靶点结合。总之,本研究为揭示槲皮素治疗 GC 的机制提供了一种新方法,将促进槲皮素在 GC 治疗中的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72c6/7486643/af48453ec170/BMRI2020-3860213.001.jpg

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