基于网络药理学及分子对接技术探讨苦参碱注射液治疗结直肠癌的作用机制  

Molecular mechanism of Matrine Injection in treating colorectal cancer based on network pharmacology and molecular docking

作　　者：何彬[1] 史刚刚[1] He Bin;Shi Ganggang(Department of Proctology,the Second Hospital of Tianjin Medical University,Tianjin 300211,China)

机构地区：[1]天津医科大学第二医院肛肠科,天津300211

出　　处：《国际生物医学工程杂志》2023年第5期439-446,共8页International Journal of Biomedical Engineering

摘　　要：目的应用网络药理学及分子对接技术探讨苦参碱注射液治疗结直肠癌的作用机制。方法从Swiss Target Prediction数据库、SuperPred数据库和中药系统药理学数据库与分析平台(TCMSP)数据库获得苦参碱的潜在靶点。从基因表达综合(GEO)数据库得到的差异基因结合GeneCards、OMIM、DrugBank和CTD数据库收集结直肠癌相关靶点。建立蛋白质-蛋白质相互作用(PPI)网络来筛选核心靶点。利用R语言的Bioconductor进行基因本体(GO)富集分析及京都基因和基因组百科全书(KEGG)信号通路分析。并通过分子对接技术评估苦参碱和核心靶点之间的相互作用。结果确定了63个苦参碱靶点,获取14198个结直肠癌疾病靶点。PPI网络的拓扑分析揭示了5个核心靶点分别为髓细胞增生蛋白(MYC)、白细胞介素-6(IL-6)、胱天蛋白酶3(CASP3)、哺乳动物雷帕霉素靶蛋白(mTOR)和双调蛋白(AR)。GO富集分析显示,生物过程(BP)主要包括过氧化氢的反应、细胞对过氧化氢的反应和细胞对化学应激的反应等;细胞组分(CC)主要包括脂筏、膜微区和突触膜等;分子功能(MF)主要包括转录协同调节因子结合、突触后神经递质受体活性和核心启动子序列特异度DNA结合等。KEGG通路富集分析表明,苦参碱的作用是由化学致癌-受体激活、肿瘤坏死因子(TNF)信号通路和Toll样受体信号通路介导的。分子对接显示苦参碱与筛选的核心靶点之间具有良好的结合能力。结论苦参碱作用MYC、IL-6、CASP3、mTOR和AR等靶点,通过调节化学致癌-受体激活、TNF信号通路和Toll样受体等信号通路发挥抗结直肠作用。Objective To explore the molecular mechanism of MatrineInjection in treating colorectal cancer based onnetwork pharmacological analysis and molecular docking.MethodsTaking matrineas the object,the corresponding potential drug targets in matrine were obtained fromSwiss Target Prediction database,and SuperPred database,and the database of traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).Differential genes were obtained fromgene expression omnibus(GEO),andGeneCards,OMIM,DrugBank,and CTD databases were used tocollect colorectal cancer-related genes.Furthermore,core targets were screened by establishing protein-protein interaction(PPI)networks.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis were performed by bioconductor of R language.Finally,the molecular docking calculation was performed to evaluate the interaction between matrine and core targets.ResultsMatrine contained 63 targets.A total of 14198 targets for colorectal cancer were obtained.The topology analysis results of the PPI network showed that 5 main targets such as myelocytomatosis proteins(MYC),interleukin-6(IL-6),Caspase-3(CASP3),mammalian target of rapamycin(mTOR),and amphiregulin(AR).GO enrichment analysis found that biological process(BP)mainly includes hydrogen peroxide reaction,cell reaction to hydrogen peroxide and cell response to chemical stress,etc;Cell components(CC)mainly include lipid rafts,membrane microregions and synaptic membranes,etc;Molecular functions(MF)mainly include transcriptional coregulatory factor binding,postsynaptic neurotransmitter receptor activity and core promoter sequence-specific DNA binding.KEGG pathway analysis showed that it involved chemical carcinogenesis-receptor activation,tumor necrosis factor(TNF)signaling pathway,and Toll-like receptor signaling pathway,etc.Molecular docking showed that matrine had good binding with the core target.ConclusionsMatrine acts on targets such as MYC,IL-6,CASP3,mTOR,and AR,and exerts therapeutic effects on c

关 键 词：苦参碱 结直肠癌 作用机制 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]