摘要
目的利用网络药理学与分子对接技术探讨吴茱萸碱治疗胃癌(GC)的分子机制。方法利用Genecards和OMIM数据库筛选GC靶点,通过Similarity ensemble approach、Swiss Target Prediction、CTD和TargetNet数据库筛选吴茱萸碱靶点,取交集后得到对应靶点,构建韦恩图对吴茱萸碱治疗GC的潜在作用靶点进行筛选,将交集靶点输入STRING数据库与Cytoscape软件得到蛋白质互作(PPI)网络,验证其相互作用关系并筛选枢纽核心靶点,分析吴茱萸碱治疗GC靶点之间的相互作用。利用R语言“ClusterProfiler”插件实现交集靶点的基因本体论(GO)功能富集分析与京都基因与基因组百科全书(KEGG)通路分析。采用Chem3D、Auto Dock Tools以及Pymol软件对吴茱萸碱及核心靶点进行分子对接验证。结果共得到14944个GC相关靶点,202个药物靶点,180个共同靶点。GO富集分析结果显示,共有2115个生物过程(BP),103个细胞组成(CC)以及208项细胞分子功能(MF)。KEGG富集分析173条KEGG信号通路,如细胞凋亡调控通路、环磷酸腺苷(cAMP)信号通路、肿瘤坏死因子(TNF)信号通路、NF-κB信号通路和IL-17信号通路等。PPI网络分析可知蛋白激酶B1(AKT1)、半胱氨酸天冬氨酸蛋白酶3(CASP3)和B细胞淋巴瘤-2基因(BCL2)等18个关键靶点在蛋白质相互作用中起枢纽作用。度值最高的前10个核心靶点为AKT1、CASP3、BCL2、信号传导与转录激活因子3(STAT3)、核因子-活化b细胞κ轻链增强子(NFKB1)、髓细胞增生原癌基因(MYC)、肿瘤坏死因子(TNF)、原癌基因酪氨酸蛋白激酶基因(SRC)、表皮生长因子受体(EGFR)、白细胞介素1B(IL1B),其分子对接结果显示枢纽节点均与吴茱萸碱有较好的亲和力。结论吴茱萸碱主要通过多靶点、多通路共同发挥治疗GC的作用。
Objective To explore the molecular mechanism of evodiamine in the treatment of gastric cancer(GC)by network pharmacology and molecular docking.Methods Genecards and OMIM databases were used to screen GC targets.Similarity ensemble approach,Swiss Target Prediction,CTD and TargetNet databases were used to screen evodiamine targets.The corresponding targets were obtained after intersection,and a Venn diagram was constructed to screen the potential targets of evodiamine in the treatment of GC.The intersection targets were input into STRING database and Cytoscape software to obtain protein interaction(PPI)network.The interaction relationship was verified and the hub core targets were screened,and the interaction between the GC targets of evodiamine treatment was analyzed.Gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of intersection targets were realized by using R language“ClusterProfiler”plug-in.Chem3 D,Auto Dock Tools and Pymol software were used to verify the molecular docking of evodiamine and core targets.Results A total of 14944 GC-related targets,202 drug targets and 180 common targets were obtained.GO enrichment analysis showed that there were 2115 biological processes(BP),103 cellular components(CC)and 208 cellular molecular functions(MF).KEGG enrichment analysis of 173 KEGG signaling pathways,such as apoptosis regulation pathway,cyclic adenosine monophosphate(cAMP)signaling pathway,tumor necrosis factor(TNF)signaling pathway,NF-κB signaling pathway and IL-17 signaling pathway.PPI network analysis showed that 18 key targets such as protein kinase B1(AKT1),cysteine aspartic protease 3(CASP3)and B-cell lymphoma-2 gene(BCL2)played a pivotal role in protein interaction.The top 10 core targets with the highest degree were AKT1,CASP3,BCL2,signal transducer and activator of transcription 3(STAT3),nuclear factor-activated b-cellκlight chain enhancer(NFKB1),myeloproliferative proto-oncogene(MYC),tumor necrosis factor(TNF),proto-oncogene tyrosine protein kinase gene(SRC),epidermal growth factor receptor(EGFR),interleukin 1B(IL1B).The molecular docking results showed that the hub nodes had good affinity with evodiamine.Molecular docking results showed that these hub nodes had a good affinity with evodiamine.Conclusion Evodiamine plays a role in the treatment of GC mainly through multi-target and multi-pathway.
作者
杨金华
刘爱群
YANG Jinhua;LIU Aiqun(Department of Gastroenterology and Respiratory Medicine&Endoscopy Center,Affiliated Tumor Hospital of Guangxi Medical University,Nanning 530021,Guangxi,China)
出处
《医学信息》
2025年第19期17-24,共8页
Journal of Medical Information
基金
广西自然科学基金区域高发疾病研究联合专项资助(编号:2023GXNSFAA026298)
广西重点研发计划(编号:桂科AB18221084、桂科AB20297021)
广西医疗卫生重点培育学科建设项目(编号:桂卫科教发〔2023〕1号)
广西医疗卫生适宜技术开发与推广应用项目(编号:S2022107)。
关键词
吴茱萸碱
胃癌
网络药理学
分子对接
Evodiamine
Gastric cancer
Network pharmacology
Molecular docking
