摘要
目的 运用网络药理学相关方法对西黄丸治疗乳腺癌的机制进行系统预测及分析。方法 通过TCMSP、中药与化学成分数据库及本草组鉴数据库检索西黄丸的相关成分及靶点,根据ADME平台筛选中药有效活性成分。检索Gene Cards、OMIM数据库获取乳腺癌的疾病靶点,并基于GEO数据库下载并分析芯片GSE33447,筛选出健康人与乳腺癌患者的差异基因。采用Cytoscape 3.7.1软件构建药物-化合物-治疗靶点网络,基于String平台绘制蛋白互作网络(PPI),采用R3.6.1软件对治疗靶点进行基因本体(gene ontology, GO)富集分析以及基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)通路分析。结果 共筛选出相关化合物106个,有效成分47个,药物疾病交集靶点76个。西黄丸治疗乳腺癌的重要成分为Quercetin、Petunidin、Morin、Beta-Sitosterol和Ellagic acid等。PPI网络显示度值排名前10位的靶基因为CASP3、EGFR、IL6、MYC、VEGFA、ESR1、CCND1、ERBB2、FOS、AR。GO富集分析得到乳腺癌相关的1277个生物学过程(BP)、85个分子功能(MF)及37个细胞组分(CC)。KEGG富集分析预测出西黄丸治疗乳腺癌可能是通过AGE-RAGE信号通路、细胞凋亡相关通路、雌激素信号通路、EGFR酪氨酸激酶抑制剂抵抗通路、低氧诱导因子-1信号通路、TNF通路及p53信号通路等关键信号通路达到治疗效果。结论 西黄丸通过多靶点、多通路的形式治疗乳腺癌,本文为进一步研究该药治疗乳腺癌的作用机制提供了理论参考。
Objective To explore the mechanism of Xihuang Pill(西黄丸)treating breast cancer based on network pharmacology.Methods Active components and corresponding targets of Xihuang Pill were obtained through Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),database of traditional Chinese medicine and chemical constituents,and database of herbs.Active components of traditional Chinese medicine were acquired according to ADME platform.Related targets of breast cancer were obtained through Gene Cards and OMIM databases.Then the chip GSE33447 was downloaded and analyzed based on the GEO database,and the differential genes between healthy people and breast cancer patients were screened out.The“drugs-component-target”network was constructed by Cytoscape3.7.1 software,and protein-protein interaction(PPI)network was drawn using STRING platform.GO enrichment analysis and KEGG pathway analysis were carried out using R3.6.1 software.Results A total of 106 compounds and 47 active components were screened out.Finally,76 drug and disease intersection targets were obtained.Quercetin,Petunidin,Morin,Beta-Sitosterol and Ellagic acid were the important components of Xihuang Pill for breast cancer.PPI network showed the degree value of the top ten target genes were CASP3,EGFR,IL6,MYC,VEGFA,ESR1,CCND1,ERBB2,FOS and AR.From GO enrichment analysis,1227 biological process terms,85 molecular functional terms and 37 cellular component terms were obtained.From KEGG pathway analysis,AGE-RAGE signaling pathway in diabetic complications,Apoptosis,Estrogen signaling pathway,EGFR tyrosine kinase inhibitor resistance,hypoxia-inducible factor-1,TNF signaling pathway,p53 signaling pathway and other related pathways were obtained.Conclusion The therapeutic effect of Xihuang Pill for breast cancer may be multi-target,multi-pathway and multi-mechanism.Our results can provide the reference for further study.
作者
来保勇
于博文
刘宇飞
余红
裴晓华
LAI Baoyong;YU Bowen;LIU Yufei;YU Hong;PEI Xiaohua(The Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing 100029,China;Xiamen Hospital of Beijing University of Chinese Medicine,Xiamen 361001,Fujian,China)
出处
《辽宁中医杂志》
CAS
2022年第10期153-159,I0001,I0002,共9页
Liaoning Journal of Traditional Chinese Medicine
基金
国家自然科学基金(817743191001982)
福建省临床重点专科项目(2022-2024)。
关键词
西黄丸
乳腺癌
生物信息学
网络药理学
差异基因
Xihuang Pill(西黄丸)
breast cancer
bioinformatics
network pharmacology
differential gene
