丙戊酸抑制恩杂鲁胺耐药前列腺癌细胞系增殖和迁移  

The proliferation and migration of valproic acid for the inhibition of enz-alutamide-resistant prostate cancer

作　　者：冯源康 黄珍林 郭阿宝 黄步登 李宁阳 卢福博 杨锦建[1] 贾占奎[1] FENG Yuan-Kang;HUANG Zhen-Lin;GUO A-Bao(Department of Urology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan,Chiha)

机构地区：[1]郑州大学第一附属医院泌尿外科,河南郑州450052 [2]天津医科大学第二医院泌尿外科

出　　处：《中国老年学杂志》2025年第3期629-636,共8页Chinese Journal of Gerontology

基　　金：国家自然科学基金面上项目(82172564)。

摘　　要：目的使用生物信息学方法探索治疗恩杂鲁胺耐药的前列腺癌的化学药物,并通过实验研究其治疗效果。方法使用生物信息学的技术分析基因表达综合数据库(GEO)数据集GSE78201和GSE143408中恩杂鲁胺耐药细胞株和对照细胞株中的差异表达基因,并对差异表达基因进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。使用蛋白质相互作用网络(STRING)数据库、Cytoscape软件获取关键基因,并对关键基因进行GO和KEGG富集分析。使用比较毒理学数据库(CTD)对关键基因的互作化学药物进行集合重叠分析。使用CCK-8法、平板克隆形成实验和Transwell实验验证关键化学药物的效果。结果差异表达分析获得差异表达基因共264个,其中下调基因96个,上调基因168个。STRING数据库、Cytoscape软件分析得到5个关键基因。使用CTD数据库分析关键基因,得出6个关键化学药物,通过CCK-8法、平板克隆形成实验和Transwell实验最终证实雌二醇和丙戊酸具有抑制恩杂鲁胺耐药前列腺癌细胞系增殖和迁移的作用。结论丙戊酸和雌二醇能够抑制恩杂鲁胺耐药前列腺癌细胞系增殖和迁移。Objective Bioinformatics technologies was used to explore chemical drugs for the treatment of enzalutamide-resist-ant prostate cancer,and its therapeutic effects were confirmed by experiments.Methods The differentially expressed genes of enzalu-tine-resistant cell lines and control cell lines in gene expression omnibus(GEO)data sets GSE78201 and GSE143408 were analyzed u-sing bioinformatics techniques,and the differentially expressed genes were enriched by gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Key genes were obtained using the protein interaction network(STRING)database to perform Cytoscape software,and GOand KEGG enrichment analysis.Comparative toxicology database(CTD)was used to perform a set overlap analysis for interacting chemicals of key genes.CCK-8 method,plate cloning formation assay and Transwell assay were used to verify the effects of key chemicals.Results A total of 264 differentially expressed genes were obtained by differential expression a-nalysis,including 96 down-regulated genes and 168 up-regulated genes.The five key genes were analyzed by STRING database and Cytoscape software.CTD database was used to analyze key genes,and 6 key chemicals were obtained.The effects of estradiol and val-proic acid on the proliferation and migration of enzalutamide-resistant prostate cancer cell lines were finally confirmed by CCK-8 meth-od,plate cloning formation assay and Transwell assay.ConclusionsValproic acid and estradiol could inhibit the proliferation and mi-gration of enzalutamide-resistant prostate cancer cells.

关 键 词：前列腺癌 恩杂鲁胺 丙戊酸 雌二醇 化学药物 

分 类 号：R697[医药卫生—泌尿科学]