天然产物研究与开发 ›› 2023, Vol. 35 ›› Issue (10): 1782-1793.doi: 10.16333/j.1001-6880.2023.10.015

• 数据研究 • 上一篇    下一篇

基于网络药理学、分子对接技术及体外实验验证探讨龙葵治疗乳腺癌的作用机制

温   馨1,胡锦航1*,程   敏1,2*,宋忠兴1   

  1. 1陕西中医药大学 陕西中药资源产业化省部共建协同创新中心 秦药特色资源研究开发国家重点实验室(培育)陕西省创新药物研究中心,咸阳 712083;2商洛学院,商洛 726000
  • 出版日期:2023-10-28 发布日期:2023-10-31
  • 基金资助:
    国家自然科学基金(82104230);陕西省科技创新团队(2022TD-56);秦岭特色生物资源综合开发利用项目(2019ZY-CXPT-09);咸阳市2020重大科技专项(2020K01-20)

Mechanism of Solanum nigrum in treatment of breast cancer based on network pharmacology,molecular docking and in vitro experimental verifcation

WEN Xin1,HU Jin-hang1*,CHENG Min1,2*,SONG Zhong-xing1   

  1. 1Shaanxi Innovative Drug Research Center,State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation) Co-construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi & Education Ministry,Shaanxi University of Chinese Medicine,Xianyang 712083,China;2Shangluo University,Shangluo 726000,China
  • Online:2023-10-28 Published:2023-10-31

摘要:

基于网络药理学和细胞实验探讨龙葵治疗乳腺癌的作用机制。利用TCMSP数据库、Swiss-Target-Prediction和文献挖掘等方法收集龙葵的活性成分7种,通过GeneCards数据库收集与乳腺癌相关靶基因110个,运用Cytoscape 3.8.0软件构建“药物-活性成分-靶点-疾病”网络,将潜在靶点导入STRING 11.5数据库中获取PPI网络,使用DAVID数据库对潜在靶点进行GO及KEGG富集分析。GO功能富集分析发现694个结果。KEGG通路富集分析发现128个结果(P < 0.05),涉及癌症、PI3K/Akt、MAPK等相关的信号通路。运用AutoDock-vina 1.1.2软件对龙葵中的7种关键活性成分,梣皮树脂醇、β-胡萝卜素、谷甾醇、薯蓣皂苷元、澳洲茄碱、胆固醇及槲皮素与潜在靶点AKT1、ESR1、EGFR、SRC、MAPK1进行分子对接,结果显示预测的关键成分薯蓣皂苷元与核心靶点AKT1和EGFR等具有较好的结合性。细胞实验结果表明,不同浓度的薯蓣皂苷元可抑制乳腺癌细胞MDA-MB-231的增殖并促进细胞凋亡,薯蓣皂苷元可调控EGFR、AKT1以及p-AKT1蛋白的表达,同时薯蓣皂苷元可下调抗凋亡蛋白Bcl-2表达、上调促凋亡蛋白Bax表达。综上结果表明,龙葵抗乳腺癌的潜在作用机制可能与调控MDA-MB-231细胞增殖及凋亡等过程相关,且通过两个关键靶基因AKT1和EGFR发挥作用。

关键词: 龙葵, 乳腺癌, 网络药理学, 分子对接, 薯蓣皂苷元, 细胞凋亡

Abstract:

To explore the mechanism of action of Solanum nigrum in the treatment of breast cancer based on network pharmacology and cellular experiments.The TCMSP database,Swiss-Target-Prediction and literature mining were used to collect seven active ingredients of S. nigrum.One hundred and ten target genes related to breast cancer were collected through the GeneCards database,and Cytoscape 3.8.0 software was used to construct the "drug-active-ingredient-target-disease" network.The potential targets were imported into the STRING 11.5 database to obtain the PPI network,and GO and KEGG enrichment analyses were performed on the potential targets using the DAVID Database.Go function enrichment analysis found 694 items.KEGG pathway enrichment analysis found 128 items (P < 0.05),involving cancer,PI3K/AKT,MAPK and other signaling pathways related to S. nigrum. Molecular docking of seven key active ingredients medioresinol,β-carotene,sitosterol,diosgenin,solanocapsine,cholesterol and quercetin from S. nigrum with potential targets AKT1,ESR1,EGFR,SRC,MAPK1,using AutoDock-vina 1.1.2 software.The molecular docking results showed that the predicted key component,diosgenin,showed good binding to the core targets,such as AKT1 and EGFR.The results showed that different concentrations of diosgenin inhibited the proliferation and promoted apoptosis of triple-negative breast cancer cells MDA-MB-231,and diosgenin regulated the expression of EGFR,AKT1 and p-AKT1 proteins,meanwhile diosgenin also down-regulated the expression of anti-apoptotic protein Bcl-2 and up-regulated the expression of pro-apoptotic protein Bax.The above results suggest that the potential mechanism of action of S. nigrum against breast cancer may be related to the regulation of MDA-MB-231 cell proliferation and apoptosis,and through two key target genes AKT1 and EGFR.

Key words: Solanum nigrum, breast cancer, network pharmacology;macromolecular docking, diosgenin, apoptosis

中图分类号:  R285