今日药学

2021, v.31(09) 658-663

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基于网络药理学与分子对接探究雷公藤内酯治疗结直肠癌的作用机制
To Explore the Mechanism of Action of Triptolide in the Treatment of Colorectal Cancer Based on Network Pharmacology and Molecular Docking

吴琪琪;郭健敏;陈伟鸿;周越菡;杨威;
WU Qiqi;GUO Jianmin;CHEN Weihong;ZHOU Yuehan;YANG Wei;College of Pharmacy,Guilin Medical University;Guangdong Lewwin Pharmaceutical Research Institute Co.,Ltd.,Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research,TCM Non-clinic Evaluation Branch of National Engineering Research Center for Modernization of Traditional Chinese Medicine,Guangdong Engineering Research Center for Innovative Drug Evaluation and Research;Hongkong University of Science and Technology;

摘要(Abstract):

目的基于网络药理学和分子对接技术探索雷公藤内酯(triptolide, TPL)治疗结直肠癌(colorectal cancer, CRC)的分子作用机制。方法分别通过Pubchem和PharmMapper数据库获得TPL的化学结构并预测药效团及作用靶点。通过GEO数据库获取CRC相关样本,进行差异表达分析。运用FunRich 3.1.3软件得到TPL作用靶点直肠癌差异基因的交集基因。通过STRING数据库和Cytoscape 3.8.2软件绘制蛋白互作(PPI)网络和筛选出关键基因。借助Metascape数据库对关键基因进行基因本体(gene ontology, GO)分子功能及基因组百科全书(Kyoto encyclopedia of genes genomes, KEGG)富集分析。通过AutoDock Vina软件进行分子对接,将对接结果采用PyMol软件绘制。结果将获得的282个TPL作用靶点与CRC显著差异的1 087个靶点取其交集,共得到32个交集靶点,经过筛选后得到10个关键基因;GO功能和KEGG通路富集分析筛选出32条信号通路,包括Ras信号通路、PI3K-Akt信号通路等;分子对接结果显示,TPL与筛选出的核心靶点结合能均<-7 kcal·mol ~(-1),由此可知结合活性显著。结论基于网络药理学及分子对接技术可以揭示TPL具有多靶点、多通路、多途径功能等特点,结果显示TPL可通过作用于CHEK1、MET、PLAU等基因调控相关信号通路,从而发挥对CRC的治疗作用。
OBJECTIVE To explore the molecular mechanism of triptolide(TPL) in colorectalcancer(CRC) based on network pharmacology and molecular docking techniques. METHODS The chemical structure of TPL was obtained from PubChem and Pharmapper databases, and the pharmacophore and target were predicted. CRC related samples were obtained from GEO database for differential expression analysis.FunRich 3.1.3 software was used to obtain the intersection genes of differential genes in rectal cancer targeted by TPL. Protein interaction(PPI) network was mapped and key genes were screened by STRING database and Cytoscape 3.8.2 software.Gene Ontology(GO) molecular function and Kyoto Encyclopedia of Genes Genomes(KEGG) enrichment analysis of key genes were performed using Metascape database.Molecular docking was performed by AutoDock Vina software, and docking results were plotted by PyMol software. RESULTS The intersection of 282 targets of TPL and 1 087 targets of colorectal cancer was obtained to get 32 intersection targets. After screening, 10 key genes were obtained. The GO function and KEGG pathway enrichment analysis screened out 32 signaling pathways, including RAS signaling pathway, PI3 K-Akt signaling pathway, etc. Molecular docking results showed that TPL had strong binding activity with the screened targets. CONCLUSION Based on network pharmacology and molecular docking, it can be revealed that TPL has the characteristics of multi-target, multi-pathway and multi-pathway function, The result shows that TPL can play an important role in the treatment of colorectal cancer by acting on the signaling pathways related to gene regulation, such as CHEK1,MET and PLAU.

关键词(KeyWords): 网络药理学;分子对接;雷公藤内酯;结直肠癌
network pharmacology;molecular docking;triptolide;colorectal cancer

Abstract:

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基金项目(Foundation): 广东省省级科技计划项目(2018B030323024);; 广东省重点领域研发计划项目(2019B020202001)

作者(Author): 吴琪琪;郭健敏;陈伟鸿;周越菡;杨威;
WU Qiqi;GUO Jianmin;CHEN Weihong;ZHOU Yuehan;YANG Wei;College of Pharmacy,Guilin Medical University;Guangdong Lewwin Pharmaceutical Research Institute Co.,Ltd.,Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research,TCM Non-clinic Evaluation Branch of National Engineering Research Center for Modernization of Traditional Chinese Medicine,Guangdong Engineering Research Center for Innovative Drug Evaluation and Research;Hongkong University of Science and Technology;

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