组蛋白去乙酰化酶抑制剂FK228对前列腺癌LNCaP细胞的抑制作用  

Inhibitory effect of histone deacetylase inhibitor FK228 on LNCaP prostate cancer cells

作　　者：孙圣坤[1] 洪宝发[1] 李秀森[2] 侯春梅[2] 肖序仁[1] 于晓妉[2] 

机构地区：[1]解放军总医院泌尿外科,北京100853 [2]军事医学科学院基础医学研究所,北京100850

出　　处：《中国临床药理学与治疗学》2007年第9期1009-1012,共4页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金重点项目(30330620);国家自然科学基金面上项目(30600613)

摘　　要：目的:研究组蛋白去乙酰化酶抑制剂FK228对前列腺癌LNCaP细胞的抑制作用机理。方法:四甲基偶氮唑蓝(MTT)检测药物对肿瘤细胞增殖的影响,hoechst33342染色观察细胞凋亡的形态学变化,Western blotting检测凋亡标志蛋白的表达,激光共聚焦分析雄激素受体(AR)蛋白的表达。结果:FK228在较低浓度即能有效抑制LNCaP细胞的增殖并诱导细胞凋亡,半效杀伤剂量(EC50)为7.4ng/mL;FK228作用24h后,细胞核内的AR基本被清除。结论:FK228能够阻断对前列腺癌细胞生长具有重要作用的AR信号通路,从而对肿瘤细胞发挥抑制作用。AIM：To investigate the mechanisms underlying the antitumor effect of histone deacetylase inhibitor FK228 on LNCaP prostate cancer cell line.METHODS：Proliferation of LNCaP cells exposed to FK228 was detected by MTT assay.Cell apoptosis was assayed by hoechst 33342 nuclei staining.Cleaved PARP,an apoptosis marker protein,was assayed by western blotting after FK228 exposure.The expression of the androgen receptor（AR） was performed by confocal laser scanning microscope.RESULTS：FK228 killed LNCaP cells with an EC50 value of 7.4 ng/mL within 48 hours exposure as well as inducing cell apoptosis.FK228 could deplete AR in the nucleus.CONCLUSION：FK228 exhibits significant antitumor effect against LNCaP cells through depletion of AR.

关 键 词：组蛋白去乙酰化酶抑制剂 前列腺癌 雄激素受体 FK228 细胞信号通路 凋亡 

分 类 号：R737.25[医药卫生—肿瘤]