Effects of dihydrotestosterone on the PAR gene expression of prostate cancer cells and the mechnism

Objective To investigate the effects and mechanism of dihydrotestosterone (DHT) on prostate androgen regulated (PAR) gene expression and probability of PAR gene as a target for prostate cancer therapy.Methods Effects of DHT at different concentrations on proliferation of LNCaP and PC3 cells were studied by means of cell counts.PAR mBNA of LNCaP cells after DHT stimulation in the pres- ence or absence of its antagonist flutamide was detected by RT-PCR.Results DHT at low concemtrations (0.001-1 nmol/L) stimulated proliferation and up-regulated PAR mRNA expression of LNCaP cells. Maximum effect occurred at 0.1 nmol/L DHT (P0.05):the cell number was (27.54±0.71)×10~4 per well and the expression of the PAR mRNA was (272.42±8.24)% of the control.DHT at concentra- tions more than 1 nmol/L inhibited the proliferation of LNCaP cells and its PAR mRNA expression:the cell number was (12.02±0.41)×10~4 per well and (11.13±1.92)×10~4 per well and the expressions of the PAR mRNA was (76.64±2.47)% and (52.97±1.07)% of controls at 10 and 100 nmol/L DHT, respectively.DHT had no significant effect on proliferation and PAR mBNA expression of PC3 cells (P0.05).The androgen receptor (AR) antagonist flutamide inhibited the stimulatory effect induced by DHT.Conclusion DHT regulates PAR mBNA expression in an AR dependent pathway.PAR gene is a potential target of gene and drugs therapy for androgen resistant prostate cancer.