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作 者:黄中强[1] 付聪[1] HUANG Zhongqiang;FU Cong(Department of Comprehensive Pharmacy,Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430014,China)
机构地区:[1]武汉市中医医院综合药学部,湖北武汉430014
出 处:《生物技术》2024年第2期179-187,共9页Biotechnology
摘 要:[目的]探究光甘草定抗乳腺癌(Breast cancer, BC)的作用机制。[方法]采用噻唑蓝(MTT)实验考证光甘草定对人乳腺癌细胞MCF-7和MDA-MB-231的抑制作用;通过PharmMapper数据库获得与光甘草定具有潜在相互作用的靶点;以“Luminal-A”和“Basal-like breast cancer”为关键词从Gene Cards数据库中下载乳腺癌相关靶点。将交集靶点导入DAVID数据库中进行富集分析,并基于STRING数据库和Cytoscape软件筛选潜在核心基因。利用GEPIA2、UALCAN和Kaplan-Meier Plotter数据库验证核心基因的表达,获取预后生物标志物并分析其泛癌性。[结果]共筛得光甘草定相关靶点286个,Luminal-A相关靶点4 285个,Basal-like相关靶点944个。光甘草定主要通过调节癌症的途径、BC通路以及PI3K-Akt通路等116条通路(P<0.05)。10个核心基因中仅MAPK1在数据库间的表达趋势不一致,且高表达的HSP90AA1与BC生存和预后不良显著正相关,并在多种肿瘤中显著高表达。[结论]光甘草定通过调控HSP90AA1等靶点和相应通路抗BC,且HSP90AA1是诊断BC的一种潜在生物标志物。[Objective]To explore the mechanism of glabridin against breast cancer(BC).[Method]The inhibitory effect of glabridin on human BC cells MCF-7 and MDA-MB-231 was verified by thiazolium blue(MTT)experiment.The potential interaction targets with glabridin were obtained through the PharmMapper database.Using"Luminal-A"and"Basal-like breast cancer"as keywords,the disease-related targets were downloaded from the Gene Cards database.The intersection of the three was imported into the DAVID database for enrichment analysis,and potential core genes were screened based on the STRING database and Cytoscape software.GEPIA2,UALCAN and Kaplan-Meier Plotter databases were used to verify the expression of core genes,obtain prognostic biomarkers and perform pan-cancer analysis.[Result]A total of 286 glabridin-related targets,4285 Luminal-A related targets,and 944 Basal-like related targets were screened.Glabridin mainly regulated 116 pathways including cancer pathway,BC pathway and PI3K-Akt pathway(P<0.05).Among the 10 core genes,only the expression of MAPK1 had inconsistent expression trends among the databases,and the high expression of HSP9OAA1 was positively correlated with the poor prognosis of BC,and it was significantly highly expressed in various tumors.[Conclusion]Glabridin treated BC by regulating HSP90AA1 and other targets and corresponding pathways,and HSP90AA1 was a potential biomarker for the diagnosis of BC.
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