基于网络药理学探讨郁金治疗肝癌的分子机制

Molecular mechanism of Turmeric in the treatment of liver cancer based on network pharmacology

目的:旨在运用网络药理学的方法预测郁金治疗肝癌的作用靶点及相关信号通路。方法:通过中药成分及中药系统药理学数据库与分析平台(TCMSP)数据库,筛选并收集郁金的活性成分及其对应的靶标。通过在线人类孟德尔网(OMIM)、人类基因组注释数据库(Genecards)和GAD数据库,收集与肝癌相关的靶标,并与药物成分所对应的靶标相比较,筛选出共同部分,获得郁金与肝癌重合的潜在靶基因。利用Cytoscape构建“化合物-靶点”作用网络,通过STRING软件构建蛋白相互作用(PPI)网络,筛选郁金治疗肝癌的关键成分与关键靶点,对关键靶点进行GO富集和KEGG富集分析分析其潜在的作用机制。结果:郁金治疗肝癌的活性成分15个,靶基因45个,药物-成分-靶点-疾病网络显示关键基因主要包括:MAPK1、MAPK3、AKT1、JUN、RELA、BCL2、CASP8、ESR1、ADRB2等。GO功能富集显示生物学过程和功能集中在辅因子结合、磷酸酶结合、酰胺结合、G蛋白偶联酰胺受体活性、抗氧化活性、类固醇活性、核受体活性、转录因子活性,直接配体调控序列特异性DNA结合、类固醇激素受体活性。KEGG功能富集显示富集较多的通路主要有乙型肝炎、人免疫缺陷病毒1感染、细胞凋亡、丙型肝炎及一些癌症信号通路。结论:郁金发挥治疗肝癌的作用可能是通过上述分子机制实现的,为后续研究及其临床应用提供理论证据。

Objective To predict the targets and related signaling pathways of turmeric in the treatment of liver cancer based on network pharmacology.MethodsThe active ingredients of turmeric and their corresponding targets were screened and collected through the traditional Chinese medicine components and systematic Chinese medicine pharmacology database and analysis platform(TCMSP)database.Through the online human Mendelian network(OMIM),the human genome annotation database(Genecards)and the GAD database,the targets related to liver cancer were collected and compared with the targets corresponding to the drug components,the common parts were screened out to obtain the potential target genes that overlap between turmeric and liver cancer.Cytoscape was used to construct the"compound-target"action network,and the protein interaction(PPI)network was constructed through STRING software to screen the key components and key targets of turmeric for the treatment of liver cancer,The GO enrichment and KEGG enrichment analysis were conducted on the key targets to analyze their potential mechanism of action.ResultsA total of 15 active components and 45 target genes in the treatment of liver cancer with turmeric turmeric were found,and the drug-component-target-disease network showed that the key genes mainly included MAPK1,MAPK3,AKT1,JUN,RELA,BCL2,CASP8,ESR1,ADRB2,etc.GO functional enrichment showed that biological processes and functions were concentrated in cofactor binding,phosphatase binding,amide binding,g-protein-coupled amide receptor activity,antioxidant activity,steroid activity,nuclear receptor activity,transcription factor activity,direct ligand regulation of sequence-specific DNA binding,and steroid hormone receptor activity.KEGG functional enrichment showed that the enriched pathways mainly included hepatitis B,human immunodeficiency virus 1 infection,apoptosis,hepatitis c and some cancer signaling pathways.ConclusionsTurmeric may treat liver cancer through the above molecular mechanism,which provids theoretical evidence for subsequent studies and clinical applications.