基于网络药理学探讨三物白散治疗胃癌的分子机制及初步验证娄余朱莹彭瑶王燚霈易书林〔摘要〕目的運用网络药理学联合分子对接探讨三物白散治疗胃癌的作用机制，通过体外细胞实验对相关靶点作初步验证。方法利用TCMSP数据库获取三物白散的活性成分及潜在靶点;通过Genecards、OMIM、TTD数据库，收集胃癌相关的作用靶点;将三物白散潜在靶点与胃癌靶点相匹配，获得三物白散抗胃癌的作用靶点，使用STRING数据库对作用靶点进行蛋白互作分析，构建PPI网络，并进行拓扑分析筛选核心靶点;用R语言对作用靶点进行GO生物学过程和KEGG通路富集分析;采用AutoDockVina软件对核心靶点与对应活性成分进行分子对接;运用qPCR验证三物白散对胃癌细胞SGC-7901中Caspase-3、Caspase-7作用靶点的调控作用。结果经筛选获得三物白散活性成分17个，三物白散作用靶点84个，经拓扑分析得到12个核心作用靶点，包括TP53、AKT1、MAPK1、JUN、CASP3等。三物白散作用靶点涉及PI3K-AKT、p53、HIF-1、IL-17等多条信号通路，通过诱导细胞凋亡、抑制细胞增殖、调节缺氧及炎性微环境发挥抗肿瘤作用。分子对接结果表明，活性成分与核心靶点有良好的结合能力。体外实验结果证实，三物白散可上调凋亡相关分子Caspase-3、Caspase-7的表达，这在一定程度上证实了网络药理学预测及指导实验设计的可靠性。结论本研究结果体现了三物白散多成分、多靶点、多通路的治疗特点，系统地揭示了其抗胃癌的药效物质、核心靶点和信号通路，为后续深入研究作用机制提供参考。〔关键词〕胃癌;三物白散;网络药理学;作用靶点;分子对接;体外细胞实验〔〕R285.5〔文献标志码〕A〔〕doi：10.3969/j.issn.1674-070X.2021.04.013〔Abstract〕ObjectiveToinvestigatethemechanismofSanwubaiPowderinthetreatmentofgastriccancerbasedonnetworkpharmacologycombinedwithmoleculardocking，andtopreliminarilyverifytherelatedtargetsbyinvitrocellexperiments.MethodsTCMSPwasusedtoscreenandpredictthecompoundsandtargetsinSanwubaiPowder.TargetsrelatedtogastriccancerwerecollectedbyGeneCards，OMIMandTTDdatabases.ThepotentialtargetsofSanwubaiPowderwerematchedwiththetargetsofgastriccancertoobtaintheanti-gastriccancertargetsofSanwubaiPowder，STRINGwasusedtoanalyzetheprotein-proteininteractionoftargets，PPInetworkwasstructuredandthenthecoretargetswerescreenedbyusingtopologyanalysis.GObiologicalprocessanalysisandKEGGpathwayenrichmentanalysiswereperformedbyRlanguage.AutoDockVinasoftwarewasusedtodockthecoretargetswiththeactiveingredients.qPCRwasusedtoverifytheregulatoryeffectsofSanwubaiPowderonthetargetsofCaspase-3andCaspase-7ingastriccancercellsSGC-7901.Results17activecomponentswerescreened，and12hubtargetsof84targetsincludingTP53，AKT1，MAPK1，JUNandCASP3wereobtainedofSanwubaiPowder.ThetargetsofSanwubaiPowderinvolvedPI3K-Akt，p53，HIF-1，IL-17signalpathways，whichplayedananti-tumorrolebyinducingcellapoptosis，inhibitingcellproliferation，regulatinghypoxiaandinflammatorymicroenvironment.Theresultsofmoleculardockingshowedthatactiveingredientshadgoodbindingcapacitywithtargets.Theresultsofinvitroexperimentsconfirmthat，SanwubaiPowdercouldup-regulatetheexpressionofapoptosis-relatedmoleculesCaspase-3andCaspase-7，whichtoacertainextentconfirmedthereliabilityofnetworkpharmacologicalpredictionandexperimentaldesignguidance.ConclusionTheresultsofthisstudyreflectedthetherapeuticcharacteristicsofSanwubaiPowderwithmultiplecomponents，multipletargetsandmultiplepathways，revealedtheactivecomponents，keytargetsandimportantpathwaysofSanwubaiPowderinthetreatmentofgastriccancer，andprovidedresearchideasandreferencebasisforfurtherdiscussiononthemechanismofaction.〔Keywords〕gastriccancer;SanwubaiPowder;networkpharmaco...