摘要
目的:利用网络药理学和分子对接法研究甘草干姜汤(LDGD)可能的抗乳腺癌活性成分及作用机制。方法:借助TCMSP数据库筛选出复方甘草干姜汤的主要有效成分;利用Genecards人类基因数据库获取乳腺癌的疾病靶点;利用STRING数据库和Cytoscape 3.8.0软件进行蛋白相互作用网络的构建和分析;并通过DAVID数据库进行GO富集分析和KEGG通路富集分析;基于文献检索甘草干姜汤的药效成分并将筛选出的关键靶点进行分子对接。结果:LDGD抗乳腺癌潜在的关键靶点有AKT1、MYC、TP53、EGF等;GO功能富集分析显示与作用靶点有关的生物学过程主要有凋亡信号通路、氧化应激等;细胞成分主要有细胞周期蛋白依赖性激酶、转录因子复合体、丝氨酸/苏氨酸蛋白激酶复合物、膜区、膜微区等;分子功能主要有蛋白质丝氨酸/苏氨酸激酶活性、转录因子活性核受体活性、泛素蛋白连接酶结合等;KEGG通路分析结果显示主要涉及p53、TNF、IL-17、EGFR、细胞凋亡等信号通路;以AKT1为靶点,8种药效成分中与其结合的小分子有甘草苷、6-姜酚、6-姜烯酚、甘草素、异甘草素、异甘草苷,其中甘草苷、6-姜酚、6-姜烯酚、甘草素的打分值大于原配体打分值的80%。结论:甘草苷、6-姜酚、6-姜烯酚、甘草素可能是甘草干姜汤中抗乳腺癌主要活性成分之一,抗肿瘤作用机制可能涉及细胞增殖、凋亡、氧化应激、炎症等相关通路。
OBJECTIVE:To investigate main active ingredients and mechanisms of licorice and candied ginger decoction(LDGD)for breast cancers by network pharmacology and molecular docking.METHODS:Main effective components of licorice and dried ginger decoction were screened using TCMSP database.Genecards database was used to obtain disease targets for breast cancer.Protein interaction networks were constructed and analyzed using STRING database and Cytoscape3.6.1 software.GO enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID database.Based on literature retrieval,the main active ingredients and key targets of LDGD were docked.RESULTS:The potential key targets of LDGD in the treatment of breast cancer included AKT1,MYC,TP53,EGF,etc.The biological processes of GO functional enrichment mainly included apoptosis signaling pathway,oxidative stress,etc.Cell components mainly included cyclin-dependent kinases,transcription factor complexes,serine/threonine protein kinase complexes,membrane regions,membrane microregions,etc.Molecular functions mainly included protein serine/threonine kinase activity,transcription factor activity,nuclear receptor activity,ubiquitin protein ligase binding,etc.KEGG pathway analyses showed that p53,TNF,IL-17,EGFR,apoptosis and other signaling pathways were mainly involved.KEGG pathway mainly involved p53,TNF,IL-17 signaling pathway,etc.AKT1 was the target and small molecule that bound to it were liquiritin,6-gingerol,6-shogaol,Liquiritigenin,Isoliquiritigenin and Isoliquiritin.The scoring values of liquiritin,6-gingerol,6-shogaol and liquiritigenin were 80%higher than that of the original ligand.CONCLUSION:Liquiritin,6-gingerol,6-shogaol and liquiritigenin might be the key anti-breast cancer components in LDGD,and the anti-cancer mechanisms might involve cell growth,apoptosis,oxidative stress,inflammation and other related signaling pathways.
作者
辛雨濛
梁桓熙
余悦华
孙震晓
XIN Yumeng;LIANG Huanxi;YU Yuehua;SUN Zhenxiao(School of Life Sciences,Beijing University of Chinese Medicine,Beijing 102488,China)
出处
《癌变．畸变．突变》
CAS
2022年第1期7-13,共7页
Carcinogenesis,Teratogenesis & Mutagenesis
基金
国家自然科学基金(81473418)。
关键词
甘草干姜汤
乳腺癌
主要活性成分
网络药理学
分子对接
licorice and dried ginger decoction
breast cancer
main active ingredient
network pharmacology
molecular docking
