Inhibitory efficacy of glucocorticoid receptor blocking on androgen-independent prostate cancer cells / 中华老年医学杂志

ABSTRACT

Objective To study the effects of glucocorticoid receptor (GR) signal pathway and downstream cytokineson androgen-independent 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 (AR),GR,HSPg0 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.