组蛋白去乙酰基酶在前列腺癌中的作用及机制研究  

The roles of histone deacetylase in prostate cancer and its mechanisms

作　　者：黄勇[1] 闫骏[1] 马敏[1] 

机构地区：[1]内蒙古医科大学附属医院泌尿外科,内蒙古呼和浩特010050

出　　处：《中国医药导报》2013年第26期13-15,共3页China Medical Herald

基　　金：国家自然科学基金自助项目(编号81260284)

摘　　要：目的研究组蛋白去乙酰基酶在前列腺癌中的作用及机制。方法采用LNCaP细胞系建立前列腺癌异种移植体动物模型,分为对照组和HDAC抑制剂组,对照组动物常规饲养,HDAC抑制剂组采用0.4%HDAC抑制剂丙戊酸(VPA)饮用水连续饮用35 d。免疫组化法检测乙酰化组蛋白H3、p21WAF1/CIP1、p27KIP1、细胞周期蛋白D1、雄激素受体(AR)表达。结果与对照组相比,HDAC抑制剂组乙酰化组蛋白H3阳性染色MOD值显著升高[(0.63±0.12)比(0.75±0.11),P<0.05],p21WAF1/CIP1[(0.27±0.06)比(0.79±0.10),P<0.05]和p27KIP1[(0.31±0.08)比(1.09±0.18),P<0.05]阳性染色MOD值显著增加,细胞周期素D1的阳性染色MOD值显著减少[(0.69±0.09)比(0.58±0.08),P<0.05],AR阳性染色MOD值显著降低[(0.62±0.10)比(0.53±0.07),P<0.05]。结论 HDAC参与前列腺癌细胞的细胞周期调控并与AR过表达有关,HDACI可通过诱导癌细胞周期阻滞及下调AR表达水平等机制抑制前列腺癌肿瘤移植体生长。Objective To explore the roles of histone deacetylase in prostate cancer and its underlying mechanisms. Methods Prostate cancer xenotransplantation animal model was established with LNCaP cell line, animals were ran- domized into control group and HDACI treatment group. Experimental animals in HDACI treatment group were treated with 0.4% VPA in drinking water for 35 days, while animals in control group were fed routinely. The acetylation status of histone H3 and expression of p21WAFI/CIP1, p27 KIP1, Cyclin D1 and AR in excised xenografts were assayed by im- munohistochemistry. Results Compared with the control group, the MOD of positive staining of acetylated histone H3 [（0.63±0.12） vs （0.75±0.11）, P 〈 0.05] and the MOD of positive staining of p21 WAFI/CIP1 [（0.27±0.06） VS （0.79±0.10）, P 〈 0.05] and p27 KIP1 [（0.31±0.08） VS （1.09±0.18）, P 〈 0.05] in HDACI treatment group significantly increased, while the MOD of positive staining of cyclin D1 [（0.69±0.09） vs （0.58±0.08）, P 〈 0.05] and AR [（0.62±0.10） vs （0.53±0.01）, P 〈 0.05] significantly reduced. Conclusion HDAC is involved in regulation of cell cycle and is associated with over-expression of AR, HDACI inhibits tumor growth by multiple mechanisms including cell cycle arrest, and inhibition of AR.

关 键 词：组蛋白去乙酰基酶 前列腺癌 丙戊酸 细胞周期 雄激素受体 

分 类 号：R737.25[医药卫生—肿瘤]