基于网络药理学探讨天然化合物色胺酮的抗肿瘤药理机制  

Antitumor pharmacological mechanism of natural compound tryptanthrin based on network pharmacology

作　　者：杨应勇 杨勇 梁妍 宋辉 张晓燕 陈岩勤 周威 YANG Ying-yong;YANG Yong;LIANG Yan;SONG Hui;ZHANG Xiao-yan;CHEN Yan-qin;ZHOU Wei(Guizhou Shenqi Institute of Pharmaceutical Research,Guizhou Shenqi Pharmaceutical Co.,Ltd.,Guiyang GUIZHOU 550004,China;School of Pharmacy,Guizhou Medical University,Gui'an New District GUIZHOU 561113,China;School of Basic Medicine,Guizhou Medical University,Gui'an New District GUIZHOU 561113,China)

机构地区：[1]贵州神奇药业有限公司贵州神奇药物研究院,贵州贵阳550004 [2]贵州医科大学药学院,贵州贵安新区561113 [3]贵州医科大学基础医学院,贵州贵安新区561113

出　　处：《中国新药与临床杂志》2024年第4期303-310,共8页Chinese Journal of New Drugs and Clinical Remedies

基　　金：贵州省科技支撑计划项目(黔科合支撑[2021]一般415);贵州省自然科学基金(黔科合基础[2020]1Y404,黔科合基础[2020]1Y380);贵州省大学生创新创业训练计划项目(201510660024);贵州医科大学教学改革研究项目(JG2021042)。

摘　　要：目的采用网络药理学方法观察天然化合物色胺酮的抗肿瘤药理机制。方法通过ADMETlab 2.0数据库对色胺酮分子的类药性进行评估,运用PharmMapper、Swiss TargetPrediction数据库预测色胺酮的作用靶点,借助OMIM数据库、DisGeNET数据库收集肿瘤疾病靶点,筛选出色胺酮抗肿瘤作用潜在蛋白靶点。利用STRING数据库、Cytoscape 3.7软件依次构建蛋白靶点之间的蛋白质-蛋白质相互作用(PPI)网络、“化合物-靶点-通路-疾病”网络;基于DAVID数据库进行GO功能富集分析、KEGG通路富集分析。采用AutoDock Vina 1.1.2软件进行分子对接,分析色胺酮与筛选出的核心靶点蛋白之间的相互作用。借助现有临床肿瘤数据库,对核心靶点开展基因表达谱交互分析。结果通过网络药理学研究共获得色胺酮抗肿瘤核心靶点158个,GO功能富集分析的生物过程与炎症反应、蛋白质磷酸化、细胞内信号转导等关联,细胞组成与胞浆、细胞质、高分子复合物等较为密切,分子功能与MAPK酶活性、ATP绑定、酶结合等相关。KEGG通路富集分析表明癌症的途径、PI3K-AKT信号通路等是色胺酮发挥抗肿瘤作用的主要途径,涉及核心靶点AKT1、PI3K、MAPK1、HSP90AA1、JAK2、NFKB1等。色胺酮与5种核心靶点AKT1、HSP90AA1、PI3K、JAK2、MAPK1之间有较好的结合活性,结合能均不超过-8.6 kcal·mol^(-1)。色胺酮抗肿瘤核心靶点的基因表达谱交互分析结果显示上述5种核心蛋白靶点均在人类肿瘤疾病发生发展中扮演重要作用。结论色胺酮通过PI3K-AKT等信号通路发挥抗肿瘤作用。AIM To clarify antitumor pharmacological mechanism of natural compound tryptanthrin by network pharmacology.METHODS The drug-likeness of tryptanthrin molecule was evaluated through ADMETlab 2.0 database.the action targets of tryptanthrin were predicted through PharmMapper and Swiss TargetPrediction database,tumor disease targets were collected by OMIM and DisGeNET database,the potential protein targets of antitumor action of tryptanthrin were then screened out.Using STRING database and Cytoscape 3.7 to sequentially construct protein-protein interaction(PPI)networks and compound target pathway disease networks between protein targets.The GO functional enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID database.AutoDock Vina 1.1.2 as a molecular docking method was used to analyze the interaction between tryptanthrin and the selected core target proteins.The gene expression profiling interactive analysis of the core targets was conducted with the existing clinical tumor database.RESULTS A total of 158 antitumor core targets of tryptanthrin were obtained by network pharmacological study,the biological processes of GO functional enrichment analysis had an association with inflammatory response,protein phosphorylation and intracellular signal transduction,etc.The cellular components were relatively close to cytosol,cytoplasm and macromolecular complex,etc.The molecular functions were associated with MAP kinase activity,ATP binding and enzyme binding,etc.The results of KEGG pathway enrichment analysis showed that pathways in cancer,PI3K-AKT signaling pathway,etc were the main pathway that tryptanthrin exerted its antitumor effect,it involved the core targets such as AKT1,PI3K,MAPK1,HSP90AA1,JAK2,NFKB1.The 5 core targets including AKT1,HSP90AA1,PI3K,JAK2,MAPK1 had good binding activities with tryptanthrin,all binding energy were less than-8.6 kcal·mol^(-1).The results of gene expression profiling interactive analysis of the core targets showed that all five core protein targets played impor

关 键 词：色胺酮 抗肿瘤药 植物 网络药理学 药理作用分子作用机制(中药) 

分 类 号：R979[医药卫生—药品]