Inhibition of Glycogen Synthase Kinase-3β Counteracts Ligand-Independent Activity of the Androgen Receptor in Castration Resistant Prostate Cancer

摘要: In order to generate genomic signals, the androgen receptor (AR) has be transported into nucleus upon androgenic stimuli. However, there is evidence from in vitro experiments that castration-resistant prostate cancer (CRPC) cells AR able translocate a ligand-independent manner. The recent finding inhibition of glycogen-synthase-kinase 3β (GSK-3β) induces rapid nuclear export androgen-stimulated prompted us analyze effects GSK-3β LNCaP sublines C4-2 and LNCaP-SSR. Both cell lines exhibit high levels absence Exposure these maleimide SB216763, potent inhibitor, resulted even under androgen-deprived conditions. Moreover, ability LNCaP-SSR grow androgens was diminished after pharmacological vitro. SB216763 modulate signalling function CRPC vivo additionally demonstrated modified chick chorioallantoic membrane xenograft assay systemic delivery SB216763. Our data suggest helps target for thereby diminishing mislocated cells. Therefore, could an interesting new strategy treatment CRPC.