Systematic Elucidation of the Mechanism of Quercetin against Gastric Cancer via Network Pharmacology Approach
Systematic Elucidation of the Mechanism of Quercetin against Gastric Cancer via Network Pharmacology Approach
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DOI：
10.1155/2020/3860213
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发表时间：
2020-09
影响因子：
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通讯作者：
Liangjun Yang;Zhipeng Hu;Jiajie Zhu;Qiting Liang;Hengli Zhou;Jiali Li;Xiangzhen Fan;Ziming Zhao-Ziming
中科院分区：
文献类型：
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作者：
Liangjun Yang;Zhipeng Hu;Jiajie Zhu;Qiting Liang;Hengli Zhou;Jiali Li;Xiangzhen Fan;Ziming Zhao-Ziming
本研究旨在阐明槲皮素治疗胃癌的可能机制。采用网络药理学方法分析了槲皮素治疗GC的靶点和途径。通过数据库挖掘获得了槲皮素抗GC的预测靶点，并通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)途径富集法分析了这些靶点与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在线工具进行HUB靶点的总体生存(OS)分析。最后，通过槲皮素与HUB靶标的分子对接，进一步分析了其作用机理。共鉴定了36个与槲皮素相关的基因，其中15个与GC相关靶点重叠。这些目标被进一步映射到319个围棋生物过程术语和10条值得注意的途径。在PPI网络分析中，确定了6个中枢目标，包括AKT1、EGFR、SRC、IGF1R、PTK2和KDR。这些指标的高表达与胃癌患者的OS不良有关。分子对接分析证实，槲皮素可以与这些HUB靶点结合。综上所述，本研究为进一步揭示槲皮素治疗胃癌的作用机制提供了一条新途径，为其在临床上的应用奠定了基础。
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, this 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.