摘要
目的联合使用网络药理学、分子对接技术和体外细胞实验探讨血府逐瘀汤治疗脑胶质瘤的活性成分及潜在作用机制。方法通过TCMSP、GeneCards等数据库预测血府逐瘀汤的作用靶点及脑胶质瘤的差异表达基因;STRING数据库构建血府逐瘀汤-脑胶质瘤蛋白互作(PPI)网络;关键靶基因进行GO及KEGG通路富集分析;Cytoscape软件构建药物-成分-靶点、药物-靶点-疾病网络;Discovery Studio软件进行分子对接验证及可视化;CCK8、EdU等生长增殖功能实验对上述生物信息学分析进行细胞实验验证。结果“药物-成分-靶点”网络表明血府逐瘀汤治疗脑胶质瘤的主要活性成分为黄芩素、汉黄芩素、β-胡萝卜素、β-谷甾醇、豆甾醇;血府逐瘀汤治疗脑胶质瘤涉及的GO生物过程包括细胞凋亡、磷酸化修饰等,涉及的KEGG通路包括高级糖基化终产物受体信号通路、致癌信号通路等;“活性成分-作用靶点-通路”网络显示血府逐瘀汤防治脑胶质瘤的核心作用靶点为PTGS2、ESR1、NOS2、GSK3β、MAPK14;分子对接结果证实主要活性成分黄芩素与核心靶点ESR1蛋白的相互作用能力较强;CCK8及EdU体外细胞实验结果表明黄芩素能够抑制胶质瘤细胞生长增殖,呈现出剂量依赖性,并在黄芩素10μmol·L^(-1)浓度时抑制效率最为显著;蛋白水平抑制ESR1的表达能够挽救黄芩素对胶质瘤细胞生长增殖的抑制(P<0.01)。结论血府逐瘀汤治疗脑胶质瘤具备多成分、多靶点、多通路的特点,其治疗机制可能通过黄芩素-ESR1发挥肿瘤抑制作用。
Objective To analyze the active ingredients and potential mechanism of Xuefu Zhuyu decoction for glioma by network pharmacology,molecular docking and in vitro cell experiment.Methods TCMSP and GeneCards databases were used to predict therapeutic targets in Xuefu Zhuyu decoction and differentially expressed genes in glioma.STRING database was used to construct the protein-protein interaction network of Xuefu Zhuyu decoction and glioma.GO and KEGG pathway enrichment analysis were performed on the target genes.The drug-ingredient-target and drug-targetdisease networks were established by Cytoscape.Molecular docking and visualization were performed by Discovery Studio software.The above bioinformatics analysis was verified by cell experiments with CCK8 and EdU functional experiments.Results The drug-ingredient-target network indicated that the main active components of Xuefu Zhuyu decoction in treating glioma included baicalin,wogonoside,beta-carotene,beta-sitosterol and daucosterol.The main biological processes in Xuefu Zhuyu decoction for glioma involved apoptosis and phosphorylation modification.The involved KEGG pathways included AGE-RAGE and carcinogenesis signaling pathways.The active ingredients-target-pathway network showed that the hub targets of Xuefu Zhuyu decoction in the prevention and treatment of glioma included PTGS2,ESR1,NOS2,GSK3βand MAPK14.Molecular docking confirmed the binding potential of the main active ingredient baicalein to the hub target ESR1.CCK8 and EdU in vitro experiments showed that baicalin inhibited the growth and proliferation of glioma cells,in a dose-dependent manner.The most effective inhibition appeared at a baicalin concentration of 10μmol·L^(-1).Inhibiting the expression of ESR1 at the protein level saved baicalein from inhibiting the growth and proliferation of glioma cells(P<0.01).Conclusion Xuefu Zhuyu decoction has multi-components,multi-targets and multi-pathways in the treatment of glioma,whose therapeutic mechanism may be tumor inhibition through baicalein-ESR1.
作者
王天翔
陈坤
陶浩军
何侠
尹丽
WANG Tian-xiang;CHEN Kun;TAO Hao-jun;HE Xia;YIN Li(The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research,Nanjing 210009;The Fourth Clinical Medical College of Nanjing Medical University,Nanjing 211166;The Collaborative Innovation Center for Cancer Personalized Medicine of Nanjing Medical University,Nanjing 211166)
出处
《中南药学》
2025年第2期423-429,共7页
Central South Pharmacy
基金
南京医科大学肿瘤个体化医学省部共建协同创新中心基金(No.JZ21449020210616)。
关键词
血府逐瘀汤
脑胶质瘤
网络药理学
分子对接
体外实验
Xuefu Zhuyu decoction
glioma
network pharmacology
molecular docking
in vitro experiment
