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基于网络药理学探讨扶正抑瘤方治疗前列腺癌的作用机制和分子靶点
甘澍,王树声,陈志强,古炽明,向松涛,李思逸,吕立国,黄芝英
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广州中医药大学第二附属医院广州 510405;广州中医药大学基础医学院广州 510000
摘要:
目的:扶正抑瘤方为临床治疗前列腺癌的自拟复方,疗效确切,已获中国发明专利授权,其药效机制尚未阐明。本文通过网络药理学方法分析初步研究扶正抑瘤方治疗前列腺癌的潜在作用机制和分子靶点,为实验研究提供思路和参考。方法:利用TCMSP数据库收集扶正抑瘤方的化合物及其靶点,利用Gencards数据库收集前列腺癌相关疾病靶点,利用STRING 11.0数据库分析扶正抑瘤方-前列腺癌共同靶点的蛋白质相互作用(PPI),利用DAVID 6.8数据库对扶正抑瘤方前列腺癌共同靶点进行基因本体论(GO)注释、富集和基因组百科全书(KEGG)通路富集,利用Cytoscape 3.8.0构建和分析扶正抑瘤方治疗前列腺癌的“方-药-化合物-靶点-通路”网络。结果:通过检索、筛选,共获得扶正抑瘤方化合物158个,化合物潜在靶点255个,前列腺癌相关疾病基因11719个,扶正抑瘤方-前列腺癌共同靶点233个。网络分析结果表明,槲皮素、山奈酚、木犀草素是扶正抑瘤方的主要活性成分,PTGS2、NCOA2、PTGS1等是扶正抑瘤方治疗前列腺癌的主要靶点,共同靶点富集于PI3K-AKT等多个信号通路,调节细胞增殖、凋亡、基因转录等生物学过程。结论:初步确定了扶正抑瘤方治疗前列腺癌的药效机制、作用网络及分子靶点,为进一步的实验研究提供了依据和参考。
关键词:  扶正抑瘤方  前列腺癌  网络药理学
DOI:10.3969/j.issn.1007-6948.2022.02.017
投稿时间:2021-08-03
基金项目:广东省自然科学基金面上项目(2021A1515011460);广东省中医药局面上项目(20211153);广东省中医院中医药科学技术研究拔尖人才专项
Network-based Mechanistic Investigation of Fuzheng Yiliu Fomula' s Treatment of Prostate Cancer
GAN Shu,WANG Shu-sheng,CHEN Zhi-qiang
Abstract:
Objective Using network-based pharmacological methods to illustrate the potential mechanisms and molecular targets by which Fuzheng Yiliu Fomula treating prostate cancer. Methods TCMSP database were searched to obtain compounds and targets of Fuzheng Yiliu Fomula. Gencards database was searched to obtain prostate cancer-related genes. The protein interaction (PPI) of the co-targets of Fuzheng Yiliu Fomula and prostate cancer were analyzed via STRING 11.0 database. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed via DAVID 6.8 database. Cytoscape 3.8.0 was employed to construct and analyze the network among fomula, drugs, compounds, targets and pathways. Results 158 compounds and 255 compound-related targets were obtained from TCMSP. 11,719 prostate cancer-related genes were downloaded from Genecards. 233 co-targets between Fuzheng Yiliu Fomula and prostate cancer were screened out. Quercetin, kaempferol and luteolin were the main active components of Fuzheng Yiliu Fomula. PTGS2, NCOA2, PTGS1 were proposed to be primary targets for Fuzheng Yiliu Fomula in treatment of prostate cancer. Co-targets were mainly enriched in PI3K-AKT signaling pathway, regulating different biological processes including cell proliferation, apoptosis and gene transcription. Conclusion The network-based mechanistic investigation has uncovered the underlying mechanisms and potential targets by which Fuzheng Yiliu Fomula treating prostate cancer. The results are useful clues for the further experimental research.
Key words:  Fuzheng Yiliu Fomula  prostate cancer  network pharmacology

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