组蛋白去乙酰基酶在前列腺癌中的作用及机制研究

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],p21 WAF1/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.

The roles of histone deacetylase in prostate cancer and its mechanisms

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.