天然产物研究与开发 ›› 2022, Vol. 34 ›› Issue (10): 1764-1773.doi: 10.16333/j.1001-6880.2022.10.015

• 开发研究 • 上一篇    下一篇

基于UPLC-Q-TOF-MS/MS和网络药理学探究茯苓抗乳腺癌作用机制

孙明杰1,王妍妍1,2,姚   亮1,2,王   雷1,2,4,6,吕婷婷1,郝丽君1,张   越1,2,6*,陈卫东1,2,3,4,5,6*


  

  1. 1安徽中医药大学药学院;2省部共建安徽道地中药材品质提升协同创新中心;3中药资源保护与开发研究所;4中药复方安徽省重点实验室;5中药饮片制造新技术安徽省重点实验室,合肥 230012;6直接口服中药饮片亳州市重点实验室,亳州 236000
  • 出版日期:2022-10-28 发布日期:2022-10-31
  • 基金资助:
    国家自然科学基金(81773988);安徽省菌类药物研发“115”产业创新团队项目(皖人才办【2020】4号);安徽省中央引导地方科技发展专项(201907d07050002);安徽高校研究生科学研究项目(YJS20210496)

Mechanism of anti-breast cancer action of Poria cocos (Schw.)Wolf based on UPLC-Q-TOF-MS/MS and network pharmacology

SUN Ming-jie1,WANG Yan-yan1,2,YAO Liang1,2,WANG Lei1,2,4,6,LYU Ting-ting1,HAO Li-jun1,ZHANG Yue1,2,6*,CHEN Wei-dong1,2,3,4,5,6*   

  1. 1School of Pharmacy,Anhui University of Chinese Medicine;2MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials;3Institute of Traditional Chinese Medicine Resources Protection and Development;4Anhui Province Key Laboratory of Chinese Medicinal Formula;5Anhui Province Key Laboratory of Traditional Chinese Medicine Decoction Pieces of New Manufacturing Technology,Hefei 230012,China;6Bozhhou Key Laboratory of Oral Chinese Herbal Slices,Bozhou 236000,China
  • Online:2022-10-28 Published:2022-10-31

摘要:

本研究结合UPLC-Q-TOF-MS/MS技术和网络药理学探究茯苓抗乳腺癌的作用机制,并通过细胞实验初步验证。基于UPLC-Q-TOF-MS/MS数据获取茯苓活性成分37个,通过数据库获取成分靶点301个。联合GEO数据库筛选出乳腺癌差异基因725个,进而获得茯苓治疗乳腺癌的潜在作用靶点30个。PPI分析发现茯苓抗乳腺癌主要作用于PPARG、PPARA等靶点。KEGG富集分析发现其发挥作用主要与PPAR信号通路相关。分子对接显示,核心成分与核心靶点对接稳定,且核心成分相应碳链上的羧基、羟基及酯基是靶点结合的主要功能基团。细胞验证实验结果表明,茯苓提取物能明显抑制乳腺癌细胞的增殖与迁移,同时降低细胞中乳酸含量;细胞免疫荧光结果表明PPARG蛋白主要分布在细胞核上,且经茯苓提取物刺激后荧光强度明显增强。综上,初步研究茯苓对乳腺癌的多靶点、多通路治疗作用,其机制可能与调节PPARG等靶点,抑制肿瘤细胞增殖及迁移,影响肿瘤细胞代谢等有关。

关键词: 茯苓, 乳腺癌, 网络药理学, UPLC-Q-TOF-MS/MS, 作用机制

Abstract:

This study combined UPLC-Q-TOF-MS/MS technology with network pharmacology to explore the anti-breast cancer mechanism of Poria cocos,and verified by cellular experiments for preliminary.There were 37 active components obtained from UPLC-Q-TOF-MS/MS data,then obtained 301 target components from drug database.A total of 725 differential genes were screened by breast cancer gene expression microarray through the GEO databases.After taking the intersection,30 potential targets of P. cocos in the treatment of breast cancer were obtained.PPI analysis showed that P. cocos mainly acted on PPARG,PPARA and other targets of anti-breast cancer.KEGG enrichment analysis showed that it was mainly related to PPAR signaling pathway.Molecular docking showed that the core components docked with the core targets stably,and the carboxyl,hydroxyl and ester groups on the corresponding carbon chains of the core components were the main functional groups for the binding targets.The results of the cell validation experiments showed that the P. cocos extract group could significantly inhibit the proliferation and migration of breast cancer cells,and obviously enhanced the fluorescence intensity of PPARG protein,which mainly distributed in the nucleus.In conclusion,this paper presents a preliminary study on the multi-target and multi-pathway therapeutic effect of P. cocos on breast cancer,the mechanism of which may be related to the regulation of PPARG and other targets,the inhibition of tumor cell proliferation and migration,and the influence of tumor cell metabolism.

Key words: Poria cocos, breast cancer, network pharmacology, UPLC-Q-TOF-MS/MS, mechanism

中图分类号:  R285.5