摘要
目的运用网络药理学分析解郁消癥颗粒治疗乳腺癌的关键靶点及作用机制。方法应用TCMSP、BATMAN-TCM、OMIM和GeneCard数据库检索解郁消癥颗粒的活性成分及其潜在的乳腺癌相关靶点,构建蛋白质-蛋白质相互作用网络。运用Metascape数据库进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)途径分析,通过分子对接研究活性化合物与潜在靶标之间的相互作用。结果GO富集分析结果显示,解郁消癥颗粒干预乳腺癌的生物过程主要包括细胞外调节蛋白激酶(ERK1/2)、细胞应激反应、细胞增殖周期、细胞凋亡、细胞黏附、细胞内信号转导、细胞因子-细胞相互作用、白细胞激活、淋巴细胞激活及水解酶活性等;主要细胞成分包括细胞质核周区、膜筏、膜微区质膜蛋白复合物等,分子功能包括激酶结合、蛋白激酶结合、泛素蛋白连接酶结合、泛素样蛋白连接酶结合以及蛋白激酶活性等。KEGG通路分析结果显示,解郁消癥颗粒主要作用于内分泌耐药、表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)耐药、铂类耐药、致癌物与受体激活、细胞凋亡、小分子RNA(MicroRNAs)、黏着斑、肿瘤蛋白聚糖等;分子通路包括蛋白激活物类似物-1(Rap1)信号通路、甲状腺激素通路、叉头转录因子(FoxO)信号通路、雌激素信号通路、泌乳素信号通路、磷脂酰肌醇3激酶/蛋白激酶(PI3K-Akt)信号通路、p53信号通路以及丝裂原活化蛋白激酶(MAPK)信号通路等。结论解郁消癥颗粒可能通过多种途径作用于乳腺癌细胞的增殖、迁移、黏附、耐药等,药物关键靶基因可能是TP53、AKT1、IL1B、CCND1、ESR1、SRC和PTEN,拮抗慢性应激可能是解郁消癥颗粒干预乳腺癌的重要机制之一,值得进一步深入研究。
Objective To analyze the key targets and mechanisms of jieyuxiaozheng granule in the treatment of breast cancer by network pharmacology.Methods From Traditional Chinese Medicine Systems Pharmacology,Traditional Chinese Medicines Integrated,Online Mendelian Inheritance in Man and GeneCards databases,we retrieved the active components and potential breast cancer related targets of jieyuxiaozheng granules,and constructed a protein-protein interaction network.Metascape database was used for gene ontology(GO)enrichment analysis and kyoto encyclopedia of genes and genomes(KEGG)pathway analysis.In addition,the interaction between active compounds and potential targets was studied by molecular docking.Results GO functional enrichment analysis showed that the biological processes of jieyuxiaozheng granule intervening breast cancer mainly included extracellular regulated protein kinase(ERK1/2),cell stress response,cell proliferation cycle,apoptosis,cell adhesion,intracellular signal transduction,cytokine cell interaction,leukocyte activation,lymphocyte activation and hydrolase activity.The main cell components include cytoplasmic perinuclear region,membrane raft,membrane micro region,plasma membrane protein complex.The molecular functions mainly included kinase binding,protein kinase binding,ubiquitin protein ligase binding,ubiquitin like protein ligase binding,protein kinase activity.KEGG pathway analysis showed that the effects of jieyuxiaozheng granule on breast cancer were mainly related to endocrine resistance,epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)resistance,platinum drug resistance,carcinogen and receptor activation,apoptosis,MicroRNAs,plaque,proteoglycan.Molecular pathways included Rap1signaling pathway,thyroid hormone pathway,forkhead box protein(FoxO)signaling pathway,estrogen signaling pathway,prolactin signaling pathway,phosphatidylinositol 3kinase/protein kinase B(PI3K-Akt)signaling pathway,p53signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway.Conclusions Jieyuxiaozheng granule may act on various pathways to promote the proliferation,migration,adhesion and drug resistance of breast cancer cells.The key target genes of TP53 may be AKT1,IL1B,CCND1,ESR1,SRCand PTEN.Chronic stress related pathways may be important mechanisms of jieyuxiaozheng granule in preconditioning breast cancer.
作者
李洋
部帅
韩超
王海永
李振祥
林家茂
LI Yang;BU Shuai;HAN Chao;WANG Hai-yong;LI Zhen-xiang;LIN Jia-mao(Shandong Cancer Hospital and Institute,Shandong First Medical University and Shandong Academy of Medical Sciences,Jinan 250117,China;Scientific Research Department,The Hospital Affiliated to Shahdong University of Traditional Chinese Medicine,Jinan 250001,China)
出处
《社区医学杂志》
CAS
2022年第24期1386-1392,共7页
Journal Of Community Medicine
基金
国家自然科学基金青年项目(81904186)
关键词
乳腺癌
解郁消癥颗粒
网络药理学
柴胡
土贝母
蟾酥
breast cancer
jieyuxiaozheng granule
network pharmacology
radix bupleuri
bolbostemae paniculati bulbus
toad venom
