基于网络药理学与分子对接的蒲公英抗乳腺癌的机制研究

Network pharmacology and molecular docking-based research on the mechanism of dandelion against breast cancer

关键词:  蒲公英  乳腺癌  网络药理学  分子对接

Key words:  dandelion  breast cancer  network pharmacology  molecular docking

摘要:

[目的] 基于网络药理学和分子对接法研究蒲公英抗乳腺癌的作用机制，以期为其临床抗乳腺癌机制的阐明提供参考。[方法] 通过Batman-TCM、TCMID、TCMSP和CancerHSP数据库筛选蒲公英有效成分及其作用靶点，运用Cytoscape软件构建蒲公英有效成分与其靶点的互作网络；通过GeneCards、OMIM、TTD、DisGeNET、Pharmgkb、Malacards数据库筛选乳腺癌疾病靶点；通过STRING构建蛋白互作网络（PPI），并通过DAVID数据库对核心靶点进行GO功能注释和KEGG通路富集分析；通过Pymol软件和AntoDock软件预测结合能力。[结果] 通过4个成分靶点数据库和6个疾病数据库共筛选到10个蒲公英潜在有效成分和136个作用靶点，1856个乳腺癌疾病靶点，41个潜在靶点基因；PPI网络中得到10个蒲公英治疗乳腺癌的关键靶点，经过GO和KEGG分析后得到53条GO分析结果和12条KEGG通路，GO分析结果表明蒲公英抗乳腺癌可能与RNA聚合酶Ⅱ启动子的转录起始过程、核染色质、DNA结合等过程相关；KEGG分析结果表明蒲公英抗乳腺癌可能涉及癌症通路、含血清素的神经突触、甲状腺激素信号通路等通路；分子对接结果显示大部分蒲公英有效成分与其关键靶点都具有良好的结合活性。[结论] 蒲公英抗乳腺癌主要涉及PTGS2、PPARG、ESR1等靶点及12条信号通路，其有效成分可以通过多靶点、多途径和多机制抑制肿瘤细胞生长。

Abstract:

[Objective] To explore the mechanism of dandelion's anti breast cancer based on network pharmacology and molecular docking,in order to provide reference for clinical anti breast cancer.[Methods] To screen the effective components and targets of dandelion through Batman TCM,TCMID,TCMSP and CancerHSP databases,and the interaction network between the effective components and targets of dandelion was constructed by Cytoscape. To screen the targets for breast cancer through GeneCards,OMIM,TTD,DisGeNET,Pharmgkb and Malacards databases. The protein-protein interaction network (PPI) was constructed by STRING,and the GO function annotation and KEGG pathway enrichment analysis of the core targets were carried out by David database. The combination ability is predicted by PyMOL and antodock software.[Results] A total of 10 potential components and 136 target sites of dandelion were screened out by 4 target databases. And 1 856 target genes for breast cancer and 41 potential target genes were screened out by 6 disease databases. PPI network contains 10 target targets for the dandelion in treatment of breast cancer. After GO and KEGG analysis,53 GO analysis results and 12 KEGG pathways were obtained. GO analysis showed that the dandelion in treatment of breast cancer may be related to the transcription initiation process,nuclear chromatin and DNA binding process of RNA polymerase II promoter. KEGG analysis showed that the dandelion in treatment of breast cancer may involve cancer pathways,serotonin related synapses,thyroid hormone signaling pathways and so on. Molecular docking results showed that most of the effective components of dandelion had good binding activity with their key targets.[Conclusion] The dandelion in treatment of breast cancer mainly involves targets such as PTGS2,PPARG and ESR1 and other 12 target pathways and dandelion's effective components can inhibit the growth of cancer cells through multiple targets,pathways and mechanisms.