Prostate growth inhibition by subtype-selective alpha1-adrenoceptor antagonist naftopidil in benign prostatic hyperplasia

BACKGROUND Recently, alpha1‐adrenoceptors (α1‐ARs) have been reported to play a prominent role in the growth of a variety of cells; however, little is known about prostate growth and subtype‐specific effects on cell proliferation. We examined the role of α1d‐AR in prostate growth and the effect of subtype‐selective α1‐AR antagonist, naftopidil, which has relatively higher affinity for α1d‐AR, on prostate growth in vitro and in vivo. METHODS First, we examined the effect of naftopidil on the cell proliferation of PrEC, PrSC, and PrSMC using WST‐1 assay. Second, we performed real‐time RT‐PCR to quantify each α1‐AR subtype mRNA expression level in a benign prostate hyperplasia (BPH) model rat, which was recently established to pathologically resemble human BPH patients. In addition, naftopidil was given to this model orally for 21 days and the proliferative and apoptotic indexes measured. Third, 18 BPH patients were administered naftopidil for 12 weeks and the proliferative and apoptotic indexes were compared before and after naftopidil administration. RESULTS Naftopidil significantly inhibited cell proliferation dose‐dependently in all cell lines that expressed α1d‐AR mRNA. The expression level of α1d‐AR during the growth process of the prostate in the BPH model rat was significantly higher than that in the normal prostate (P