糖皮质激素受体阻断对雄激素非依赖性前列腺癌细胞的抑制作用

Inhibitory efficacy of glucocorticoid receptor blocking on androgen-independent prostate cancer cells

目的探讨糖皮质激素受体（GR）信号通路及下游炎症因子白细胞介素（IL-6）等在前列腺癌雄激素非依赖生长中的作用。方法体外培养人雄激素依赖性前列腺癌（ADPC）细胞株LNCaP和雄激素非依赖性前列腺癌（AIPC）细胞株DU145，免疫细胞化学检测雄激素受体（AR）、GR、热休克蛋白（HsPg0）和IL-6表达的差异，观察GR阻断剂RU486对LNCaP和DU145生长的影响，GR阻断后DU145细胞HSP90、IL-6mRNA及蛋白表达的变化。结果LNCaP细胞AR＋，GR-，而DU145细胞GR＋，AR-，DUl45细胞HSP90、IL-6表达明显强于LNCaP细胞（P〈0．01）；Ru486对LNCaP细胞生长的影响很小，而对DUl45细胞呈现出明显的浓度和时间依赖性抑制作用；RU486作用后DU145细胞中HSP90、IL-6mRNA及蛋白的表达明显降低。结论GR信号通路是DU145细胞的主要成活途径，GR信号通路的异常活化并促进炎症因子HSP90、IL-6等的高表达是前列腺癌雄激素非依赖进展的重要原因。

Objective To study the effects of glucocorticoid receptor （GR） signal pathway and downstream cytokineson androgenqndependent growth of prostate cancer （PC） cells. Methods The human androgen-dependent PC （ADPC） cell line LNCaP and androgen-independent PC （AIPC） cell line DU145 were cultured in vitro. Immunocytochemistry was used to examine the expressions of the androgen receptor fAR）, GR, HSP90 and interleukin-6 （IL-6）. The GR antagonist RU486 was used to treat cultured cells, and the effects of RU486 on the proliferation of both cell lines were analyzed by MTT assay. Expressions of HSP90 and IL-6 mRNA and protein were assessed by RT-PCR and Western blotting respectively. Results LNCaP cells were AR-positive and GR-negative, whereas DU145 cells were GR-positive and AR-negative. The expressions of HSP90 and IL-6 were significantly stronger in DU145 cells than in LNCaP cells （P^0.01）. RU486 had no obviously effects on the growth of LNCaP cells, but exerted a significant time- and dose-dependent growth inhibition on DU145 cells. RU486 treatment in DU145 cells also resulted in a dose-dependent decrease in the expressions of HSP90 and IL-6 mRNA and protein. Conclusions GR signal pathway may be the main survival pathway for DU145 cells. Abnormal hyperactivation of GR signal pathway and its promoting the expressions of HSP90 and IL-6 may contribute to the progression of ADPC to AIPC after androgen ablation.