组蛋白去乙酰化酶抑制剂FK228对前列腺癌LNCaP细胞抑制效应的细胞信号通路研究  

Targeting multiple signaling pathways in LNCaP prostate cancer cell line by histone deacetylase inhibitor FK228

作　　者：孙圣坤[1] 于晓妉[2] 史立新[1] 洪宝发[1] 张旭[1] 

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

出　　处：《现代泌尿生殖肿瘤杂志》2009年第1期32-33,60,共3页Journal of Contemporary Urologic and Reproductive Oncology

基　　金：国家自然科学基金资助项目(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细胞抑制作用的细胞信号机制。方法Western blot分析细胞蛋白乙酰化水平、细胞信号通路蛋白及细胞周期相关蛋白的表达。结果FK228能够使细胞内蛋白乙酰化水平增高,乙酰化组蛋白H3积累,多种细胞信号通路的相关蛋白如雄激素受体、HER-2、Raf-1、Akt、CDK4等呈时间依赖性和剂量依赖性被清除。结论FK228能够同时阻断对细胞生长具有重要作用的多条细胞信号通路,从而对前列腺癌LNCaP细胞发挥抑制作用。Objective To investigate the molecular mechanisms underlying the antitumor effect of histone deacetylase inhibitor FK228 on LNCaP prostate cancer cells. Methods Western blot was used to analyze protein acetylation standard as well as the expression of a panel of signaling molecules after FK228 exposure. Results FK228 exposure caused elevated acetylation of total cellular proteins as well as accumulation of acetylated H3. In addition, signaling molecules which play key roles in prostate cancer such as AR, HER-2, Raf-1 ,CDK4, and Akt were depleted by FK228 in a dose and time-dependent manner. Conclusions FK228 exhibits significant antitumor activity against LNCaP cells by simultaneously interfering with multiple signaling pathways such as HER-2/MAPK, AR, and PI-3K-Akt pathways.

关 键 词：组蛋白脱乙酰基酶 前列腺肿瘤 细胞信号通路 组蛋白去乙酰化酶抑制剂 FK228 

分 类 号：R737.25[医药卫生—肿瘤]