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网络药理学揭示雷公藤治疗鼻咽癌的作用机制。

Network Pharmacology to Uncover the Molecular Mechanisms of Action of LeiGongTeng for the Treatment of Nasopharyngeal Carcinoma.

机构信息

Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Radiation Oncology Clinical Medical Research Center of Guangxi, Nanning, Guangxi, China (mainland).

出版信息

Med Sci Monit Basic Res. 2020 May 25;26:e923431. doi: 10.12659/MSMBR.923431.

DOI:10.12659/MSMBR.923431
PMID:32448862
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7268886/
Abstract

BACKGROUND Nasopharyngeal carcinoma (NPC) is a common head and neck cancer epidemic in southern China and southeast Asia. LeiGongTeng has been widely used for the treatment of cancers. The purpose of this study was to determine the pharmacological mechanism of action of LeiGongTeng in the treatment of NPC using a network pharmacological approach. MATERIAL AND METHODS The traditional Chinese medicine systems pharmacology (TCMSP) database was used to identify active ingredients and associated target proteins for LeiGongTeng. Cytoscape was utilized to create a drug-disease network and topology analysis was conducted to analyze the degree of each ingredient. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) online tool was applied for the construction and analysis of the protein-protein interaction (PPI) network, while Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) functional analyses were utilized to determine drug-disease common genes. RESULTS 22 active ingredients including kaempferol, nobiletin, and beta-sitosterol, and 30 drug-disease common genes including VEGFA, CASP3, ESR1, and RELA were identified. GO analysis indicated that 94 biological processes, including RNA polymerase II, apoptotic process, response to drug, cell adhesion, and response to hypoxia, were found to be associated with NPC. The KEGG enrichment analysis showed that 58 pathways, including the PI3K-Akt signaling pathway, microRNAs in cancer, tumor necrosis factor (TNF) signaling pathway and pathways in cancer were found to be associated with NPC. CONCLUSIONS LeiGongTeng exerts its therapeutic effect through various biological processes and signaling pathways since it acts on several target genes. Systematic pharmacology can be used to predict the underlying function of LeiGongTeng and its mechanism of action in NPC.

摘要

背景

鼻咽癌(NPC)是中国南方和东南亚地区常见的头颈部癌症。雷公藤被广泛用于癌症的治疗。本研究旨在采用网络药理学方法确定雷公藤治疗 NPC 的药理作用机制。

材料和方法

使用中药系统药理学(TCMSP)数据库识别雷公藤的活性成分和相关靶蛋白。使用 Cytoscape 创建药物-疾病网络,并进行拓扑分析以分析每个成分的程度。使用 Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) 在线工具构建和分析蛋白质-蛋白质相互作用(PPI)网络,同时利用京都基因与基因组百科全书(KEGG)通路富集和基因本体论(GO)功能分析确定药物-疾病共同基因。

结果

鉴定出 22 种活性成分,包括山奈酚、诺比汀和β-谷甾醇,以及 30 种药物-疾病共同基因,包括 VEGFA、CASP3、ESR1 和 RELA。GO 分析表明,有 94 个生物学过程与 NPC 相关,包括 RNA 聚合酶 II、凋亡过程、药物反应、细胞黏附和低氧反应。KEGG 富集分析表明,有 58 条通路与 NPC 相关,包括 PI3K-Akt 信号通路、癌症中的 microRNAs、肿瘤坏死因子(TNF)信号通路和癌症通路。

结论

雷公藤通过多种生物过程和信号通路发挥治疗作用,因为它作用于几个靶基因。系统药理学可用于预测雷公藤的潜在功能及其在 NPC 中的作用机制。

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