雄激素共激活物DDC在氟他胺对前列腺癌细胞LNCaP作用中的表达变化  

Change of expression of the androgen receptor coactivator DDC in the effect of flutamide on prostate cancer cell LNCaP

作　　者：邵晨[1] 汪涌[1] 师长宏[2] 张运涛[1] 刘凡[3] 王禾[1] 

机构地区：[1]第四军医大学西京医院泌尿外科,西安710032 [2]第四军医大学动物实验中心 [3]第四军医大学唐都医院泌尿外科

出　　处：《中华实验外科杂志》2005年第9期1040-1042,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目(30100185);全军医药卫生科研基金项目(01Q120)

摘　　要：目的观察雄激素受体(AR)共激活物DDC在氟他胺对前列腺癌雄激素敏感细胞系LNCaP的作用的表达变化。方法噻唑蓝比色法(MTT),流式细胞术等技术,研究氟他胺对LNCaP细胞的作用,并使用基因芯片对其DDC在其中的作用作了初步探讨。结果LNCaP细胞在7d内受到氟他胺的刺激而加速生长,但5代后细胞增殖受到抑制。此种效应与剂量相关。细胞增殖主要被阻断于G1/S期。其相关机制主要是AR共激活物DDC的表达受到抑制。结论氟他胺对LNCaP的作用为双向,即在低浓度和较短作用时间内为增殖,在高浓度和较长作用时间后为抑制。此种抑制效应可能是通过抑制DDC的表达,影响下游细胞周期相关基因的表达,从而阻断细胞周期于G1/S调控点。Objective To investigate the expression of androgen receptor coactivator DDC in the effect of flutamide on the prostate cancer cell line-LNCaP. Methods MTT and flow cytometer were employed to explore the effect of flutamide on LNCaP, and cDNA microarrays were performed to elucidate DDC＇s expression in this process. Results The LNCaP ceils＇ growth accelerated within 7 days after hydmxyflutamide treatment. However, it was inhibited after 5 generations. And this inhibition was correlated with the dosage treated. The ceil cycle was blocked mainly in Gl phase. The correlated molecular mechanism was the down-regulation of the androgen receptor coactivator DDC. Conclusion Hydroxyflutamide could stimulate LNCaP ceil within several days. However, with the drug-treating time prolonging, the stimulation effect switched to inhibition, which is due to the inhibition of DDC＇ s expression, influencing the expression of its correlated downstream ceil cycle related genes, thus blocking cell cycle in G1/S checkpoint.

关 键 词：前列腺癌 雄激素 基因芯片 LNCAP细胞 前列腺癌细胞 雄激素受体 表达变化 氟他胺 DDC 激活物 

分 类 号：R737.25[医药卫生—肿瘤]