首页|基于网络药理学和实验验证探讨中药枇杷叶抑制三阴性乳腺癌的分子机制

基于网络药理学和实验验证探讨中药枇杷叶抑制三阴性乳腺癌的分子机制

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目的:基于网络药理学和实验验证探讨中药枇杷叶抑制三阴性乳腺癌的分子机制.方法:通过TCMSP数据库获取中药枇杷叶的潜在药效成分及靶点.利用GeneCards、OMIM及DisGeNET数据库获取三阴性乳腺癌的相关靶点.利用String平台进行蛋白互作分析.采用Metascape数据库分析潜在靶点参与的生物过程及通路.通过CB-Dock进行分子对接验证.采用MTT比色法和平板克隆形成实验检测中药枇杷叶潜在药效成分对4T1细胞增殖活性的影响.采用蛋白免疫印迹法检测相关蛋白表达水平.结果:中药枇杷叶有18个潜在药效成分和147个潜在靶点作用于三阴性乳腺癌.齐墩果酸(olea-nolic acid,OA)和(-)-表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)等成分与TP53和AKT1等靶点的亲和力强.OA和EGCG可以时间和剂量依赖的方式抑制4T1增殖,减少p-AKT、p-mTOR蛋白表达,并上调细胞周期调控因子p27的表达水平.结论:中药枇杷叶中的OA和EGCG可以通过调节PI3K-AKT信号通路,上调细胞周期调控因子p27,抑制三阴乳腺肿瘤细胞的侵袭和复制,从而抑制乳腺癌细胞增殖.
Molecular mechanism of Eriobotryae Folium against triple-negative breast cancer based on network phar-macology and experimentation
OBJECTIVE To explore the mechanism of Eriobotryae Folium on triple-negative breast cancer based on network pharmacology and experimentation.METHODS The TCMSP database was used to obtain the main chemical constituents and targets of Eriobotryae.GeneCards,OMIM,and DisGeNET database were used to obtain the relevant targets for triple-negative breast cancer.Protein-protein interaction analysis was performed by String platform.Metascape database was used to analyze the biological processes and pathways involved in the potential targets of Eriobotryae,and molecular docking validation was performed by CB-Dock.The influence of potential pharmacological components of Eriobotryae on the proliferative activity of 4T1 cells was examined by MTT assay and plate clone formation assay.The related protein expression levels were detected by Western Blot.RESULTS Eighteen potential active components and 147 potential targets of Eriobotryae against triple-negative breast cancer were identified.Oleanolic acid(OA),(-)-epigallocatechin gallate(EGCG),and other components of Eriobotryae showed a strong affinity with targets such as TP53 and AKT1.OA and EGCG inhibited 4T1 proliferation,reducing p-AKT,p-mTOR pro-tein expression and upregulating the cell cycle regulator p27 expression level in a time-and dose-dependent manner.CONCLUSION OA and EGCG in Eriobotryae suppress the invasion and replication of triple-negative breast cancer cells by regulating the PI3K-AKT signaling pathway and upregulating the cell cycle regulator p27 to achieve anti-proliferation of breast can-cer cells.

Eriobotryae Foliumtriple-negative breast cancernetwork pharmacologymolecular mechanism

杨渊、谈相云、邱振鹏、肖晗

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华中科技大学同济医学院附属武汉儿童医院(武汉市妇幼保健院)妇女儿童健康研究所,湖北武汉 430016

湖北中医药大学药学院,湖北武汉 430065

枇杷叶 三阴性乳腺癌 网络药理学 分子机制

武汉市卫生健康委武汉市医学科研项目武汉市卫生健康委武汉市医学科研项目

WZ19Q14WZ20A09

2024

中国医院药学杂志
中国药学会

中国医院药学杂志

CSTPCD北大核心
影响因子:1.198
ISSN:1001-5213
年,卷(期):2024.44(4)
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