摘要
目的:采用网络药理学方法研究参苓扶正方治疗胃癌的生物学物质基础及其药效机制。方法:借助中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、GeneCards等数据库及相关文献构建参苓扶正方(主要药物为人参、半夏、黄连、茯苓、白术)治疗胃癌的"药物-疾病-靶点"网络,利用STRING及CentiScape插件构建上述药物治疗胃癌的蛋白-蛋白相互作用(protein-protein interaction,PPI)网络,同时对关键靶点进行基因本体(Gene Ontology,GO)功能富集分析以及京都基因与基因组百科全书通路富集(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析,并以细胞实验进一步验证网络药理学所得结论。结果:参苓扶正方治疗胃癌的"药物-疾病-靶点"网络共涉及139个共同靶点,GO功能富集提示参苓扶正方治疗胃癌的生物学过程及功能集中在泛素化、核受体功能、转录相关功能、激素受体功能、细胞凋亡、细胞周期等;KEGG通路富集分析提示参苓扶正方治疗胃癌主要涉及细胞凋亡、细胞周期、肿瘤抑制信号通路(p53)、内分泌抵抗、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)、肿瘤坏死因子(TNF)等信号通路。细胞实验结果显示,参苓扶正方可有效抑制胃癌BGC-823细胞的增殖并促进其凋亡。Western blotting结果显示参苓扶正方能够调控胃癌BGC-823细胞增殖、凋亡以及细胞周期相关蛋白的表达水平。结论:参苓扶正方治疗胃癌的作用靶点和药效机制,可能与其调控细胞增殖、凋亡和细胞周期的生物学过程及信号通路相关。
OBJECTIVE To explore the biological material basis and pharmacodynamic mechanism of Shenling Fuzheng Decoction in the treatment of gastric cancer through network pharmacology.METHODS With the aids of TCMSP(Traditional Chinese Medicine Systems Pharmacology Database&Analysis Platform),GeneCards and the related literatures,Shenling Fuzheng Recipe was constructed(major ingredients of ginseng,pinellia,coptis,poria¯oce)with a"drug-disease-target"network,using STRING and CentiScape plug-ins for constructing a protein-protein interaction(PPI)network for the treatment of gastric cancer and performing GO(Gene Ontology)functional enrichment analysis and KEGG(Kyoto Encyclopedia of Genes and Genomes)signaling pathway enrichment analysis and cell experiments were employed to further verify the findings of network pharmacology.RESULTS The"drug-disease-target"network of Shenling Fuzheng Decoction for treating gastric cancer involved 139 common targets.The enrichment of GO function indicated that biological process and function of Shenling Fuzheng Decoction were due to ubiquitination,nuclear receptor,transcription-related,hormone receptor,cell apoptosis and cell cycle,etc.;KEGG pathway enrichment analysis revealed that cell apoptosis,cell cycle,tumor suppressor signaling pathway(p53),endocrine resistance,phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT),tumor necrosis factor(TNF)and other signaling pathways contributed to its actions.Cell experiment indicated that this Decoction could effectively suppress the proliferation of gastric cancer BGC-823 cells and promote their apoptosis.And Western blot confirmed that this Decoction regulated the proliferation and apoptosis of gastric cancer BGC-823 cells and the expression of cell cycle-related proteins.CONCLUSION The targets and pharmacodynamic mechanism of Shenling Fuzheng Decoction in the treatment of gastric cancer may be correlated with the biological processes and signal pathways of regulating cell proliferation,apoptosis and cell cycle.
作者
刘伟
李为
杨磊
李媛
吴娟
LIU Wei;LI Wei;YANG Lei;LI Yuan;WU Juan(Hunan University of Traditional Chinese Medicine,Hunan Changsha 410208,China;First Affiliated Hospital,Hunan University of Traditional Chinese Medicine,Hunan Changsha 410000,China)
出处
《中国医院药学杂志》
CAS
北大核心
2021年第4期335-341,共7页
Chinese Journal of Hospital Pharmacy
基金
国家自然科学基金项目(编号:81804075)
湖南省自然科学基金项目(编号:2018JJ50436)
湖南省科技厅科学技术项目(编号:20180651)
湖南省哲学社会科学基金年度项目(编号:17YBA322)。
关键词
参苓扶正方
胃癌
网络药理学
药效机制
"药物-疾病-靶点"网络
Shenling Fuzheng Recipe
gastric cancer
network pharmacology
pharmacodynamic mechanism
"drug-disease-target"network
作者简介
刘伟,女,硕士研究生,讲师,研究方向:中医药信息化处理相关研究。
