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中国临床药理学与治疗学 ›› 2023, Vol. 28 ›› Issue (12): 1321-1330.doi: 10.12092/j.issn.1009-2501.2023.12.001

• 基础研究 • 上一篇    下一篇

基于网络药理学探讨平消胶囊通过AKT1/β-catenin信号促进乳腺癌凋亡的作用机制

陈洪晓1,2,刘  苏2,金  乐2,张慧慧3,张  蕾2,陈昭琳1,2   

  1. 1安徽医科大学药学院,合肥  230032,安徽;2中国科学技术大学附属第一医院(安徽省立医院)药学部,合肥  230001,安徽;3安徽医科大学临床药理研究所,抗炎免疫药物教育部重点实验室,合肥  230032,安徽

  • 收稿日期:2023-06-21 修回日期:2023-08-07 出版日期:2023-12-26 发布日期:2023-12-21
  • 通讯作者: 陈昭琳,女,博士,硕士生导师,主管药师,研究方向:临床药学和肿瘤药理学。 E-mail: czl0808@ustc.edu.cn
  • 作者简介:陈洪晓,男,硕士,研究方向:临床药学和肿瘤药理学。 E-mail: chx880727@163.com
  • 基金资助:
    安徽省自然科学基金项目(2208085MH252);安徽省重点研究与开发计划项目(201904a07020092);安徽省自然科学基金项目(2108085MH311)

Mechanism of Pingxiao capsule promoting breast cancer apoptosis through AKT1/β-catenin signal based on network pharmacology

CHEN Hongxiao 1,2, LIU Su 2, JIN Le 2, ZHANG Huihui 3, ZHANG Lei 2, CHEN Zhaolin 1,2   

  1. 1 School of Pharmacy Anhui Medical University, Hefei 230032, Anhui,  China; 2 The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui, China; 3 Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Hefei 230032, Anhui, China
  • Received:2023-06-21 Revised:2023-08-07 Online:2023-12-26 Published:2023-12-21

摘要:

目的:探究平消胶囊治疗乳腺癌的潜在作用机制。方法:利用TCMSP、TCM-ID、GeneCards等数据库筛选平消胶囊与乳腺癌的相关靶点;Cytoscape软件构建“药物-靶点-疾病”网络;运用R软件进行GO和KEGG分析;使用Autodock Vina和Pymol软件进行平消胶囊活性成分与核心靶点的分子对接及可视化;通过R软件survival包对核心靶点进行分析,筛选出与总体生存时间密切相关的基因;通过CCK-8法检测细胞活力;流式细胞术检测细胞凋亡;Western blot检测p-AKT1、β-catenin和cyclinD1的蛋白表达水平。结果:筛选出药物靶点194个,疾病靶点1 612个,韦恩图求交集靶点共127个,核心靶点主要包括TB53、AKT1、TNF、CASP3等20个;GO分析主要与氧化应激反应、细胞对化学反应的调控等生物活性有关;KEGG分析主要通过PI3K-AKT信号通路、TNF信号通路、IL-17信号通路等通路有关;分子对接结果显示活性成分与核心靶点AKT1、MAPK1、RELA均有较好的结合;细胞实验表明槲皮素(40、80、120 μmol/L)促进乳腺癌细胞凋亡;Western blot检测显示随着不同浓度的槲皮素处理乳腺癌细胞48 h后,p-AKT1、β-catenin和cyclinD1的蛋白表达量均不同程度地降低。结论:网络药理学与细胞实验证实平消胶囊可能通过调节AKT1/β-catenin信号通路,发挥其抗乳腺癌作用。

关键词: 平消胶囊, 乳腺癌, 网络药理学, 分子对接, AKT1/β-catenin

Abstract:

AIM: To explore the potential mechanism of action of Pingxiao capsule in the treatment of breast cancer. METHODS: TCMSP, TCM-ID, GeneCards and other databases were used to screen the related targets of Pingxiao capsule and breast cancer. Cytoscape software builds drug-target-disease networks. R software was used for GO and KEGG analysis. Autodock Vina and Pymol software were used for molecular docking and visualization of Pingxiao capsule active ingredients and core targets. Core targets were analyzed by R software survival package, and genes closely related to overall survival time were screened out. Cell viability was detected by CCK-8 method. Flow cytometry was used to detect cell apoptosis. The protein expression levels of p-AKT1, β-catenin and cyclinD1 were detected by Western blot. RESULTS: A total of 194 drug targets were screened, 1612 disease targets were identified, 127 intersection targets were identified by Venn diagram, and 20 core targets were TB53, AKT1, TNF, CASP3, etc. GO analysis was mainly related to oxidative stress response, cell regulation of chemical reaction and other biological activities. KEGG analysis was mainly related to PI3K-AKT signaling pathway, TNF signaling pathway, IL-17 signaling pathway and other pathways. Molecular docking results showed that the active constituents were well combined with the core targets AKT1, MAPK1 and RELA. Cell experiments showed that quercetin (40, 80, 120 μmol/L) promoted apoptosis of breast cancer cells. Western blot analysis showed that the protein expressions of p-AKT1, β-catenin and cyclinD1 decreased with different concentrations of quercetin treated for 48h. CONCLUSION: Network pharmacology and cell experiments confirmed that Pingxiao capsule may exert its anti-breast cancer effect by regulating AKT1/β-catenin signaling pathway. 

Key words: Pingxiao capsule, breast cancer, network pharmacology, molecular docking, AKT1/β-catenin

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