摘要
基于网络药理学探索中药薏苡仁治疗乳腺癌的活性成分、潜在靶点及分子机制研究。在TCMSP数据库筛选薏苡仁的有效成分,Swiss Target Prediction数据库检索有效成分对应的靶点,同时检索Genecards、OMIM、TTD、Drugbank获得乳腺癌的相关基因,经交集后可获得薏苡仁作用于乳腺癌的候选靶基因。借助Cytoscape3.7.2构建"药物-化合物-靶点-疾病"网络,在STRING平台构建PPI网络。利用Metascape平台对候选基因进行GO注释和KEGG通路富集分析,并构建"通路-靶点"网络,以进一步筛选关键基因与有效成分。在i Bio Tools平台筛选差异表达的候选靶基因。共得到活性成分9个,候选靶点58个,GO分析涉及526个生物过程、84个分子功能、37个细胞组分和KEGG通路136条。薏苡仁治疗乳腺癌的有效成分为豆甾醇、谷甾醇α1、亚油酸乙酯和2-十八烯酸单甘油酯等;关键靶点为CYP19A1、AR、PTPN1、HMGCR、CYP17A1等。GO功能包括影响蛋白激酶活性和细胞膜;KEGG则主要涉及癌症相关、雌激素、癌症蛋白聚糖信号通路。较健康人群差异表达基因中PPARG、FABP4等12个基因上调,CDK1、TOP2A等11个基因下调。该研究揭示了薏苡仁治疗乳腺癌的分子生物学机制,为后续中医药潜在抗肿瘤作用的研发提供了新的依据与方向。
To investigate the effective components,potential targets and molecular mechanism of coix seed in the treatment of breast cancer based on network pharmacology,effective components of coix seed were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).And the targets of above components were screened by Swiss Target Prediction Database.The related genes of NSCLC were obtained by searching the Human Gene Database(Gene Cards),Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD)and Drug bank database.The candidate targets of coix seed in the treatment of breast cancer were obtained after extracting the intersection network.The"drug-component-target-disease"network was built by virtue of Cytoscape3.7.2 and the Protein-protein Interaction networks were constructed on the STRING platform.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of candidate genes were performed using Metascape platform,and the"pathway-target"network was constructed to further screen key genes and active components.The candidate target genes differentially expressed were screened on i Bio Tools platform.A total of 9 components,58 candidate targets,206 biological process,84 molecular functions,37 cellular components,136 KEGG pathways and 23 differential expression genes were obtained.The active components of coix seed in the treatment of breast cancer are sitosterol alpha1,mandenol and 2-monoolein.The key targets are CYP19 A1、AR、PTPN1、HMGCR、CYP17 A1.The core GO functions fasten on protein kinase activity and cell membrane;KEGG mainly involves pathways in cancer,estrogen signaling pathway and proteoglycans in cancer.Compared with healthy people,12 genes such as PPARG and FABP4 were up-regulated,while 11 genes such as CDK1 and TOP2 A were down-regulated.This study revealed the molecular biological mechanism of coix seed in the treatment of breast cancer and provided a new basis and direction for the subsequent research and developmen
作者
樊舒瑶
沈泳
谢小红
FAN Shu-yao;SHEN Yong;XIE Xiao-hong(Zhejiang University of Traditional Chinese Medicine,Hangzhou 310053,China;No.1 Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine,Hangzhou 310006,China)
出处
《药物生物技术》
2021年第3期245-253,共9页
Pharmaceutical Biotechnology
基金
国家自然科学青年基金(No.81902046)。
关键词
乳腺癌
中药
薏苡仁
抗癌
网络药理学靶点
Breast cancer
Herbal prescriptions
Coix seed
Anti-cancer
Network pharmacology
Target