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Prostate growth inhibition by subtype-selective alpha(1)-adrenoceptor antagonist naftopidil in benign prostatic
Yoshiyuki Kojima1, Shoichi Sasaki, Nobuyuki Oda
1Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan. ykojima@med.nagoya-cu.ac.jp
Background:
Recently, alpha(1)-adrenoceptors (alpha(1)-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 alpha(1d)-AR in prostate growth and the effect of subtype-selective alpha(1)-AR antagonist, naftopidil, which has relatively higher affinity for alpha(1d)-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 alpha(1)-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 alpha(1d)-AR mRNA. The expression level of alpha(1d)-AR during the growth process of the prostate in the BPH model rat was significantly higher than that in the normal prostate (P < 0.001). Naftopidil administration inhibited cell proliferation without apoptosis in the BPH model rat and BPH patients.
Conclusions:
alpha(1d)-AR may play an important role in the regulation of cellular proliferation in the prostate, and alpha(1d)-AR blockage by naftopidil may not only improve lower urinary tract symptoms but also inhibit prostate growth in BPH patients.
Insights
Alpha(1d)-adrenoceptors (alpha(1d)-AR) are crucial for prostate growth. Blocking alpha(1d)-AR with naftopidil inhibits prostate cell proliferation in benign prostate hyperplasia (BPH) patients and models.
Area of Science:
- Pharmacology
- Urology
- Cell Biology
Background:
- Alpha(1)-adrenoceptors (alpha(1)-ARs) influence various cell growths.
- The specific role of alpha(1d)-AR in prostate growth and proliferation remains unclear.
- Naftopidil, an alpha(1)-AR antagonist with higher affinity for alpha(1d)-AR, was investigated.
Purpose of the Study:
- To investigate the role of alpha(1d)-AR in prostate growth.
- To evaluate the effect of naftopidil on prostate cell proliferation in vitro and in vivo.
- To assess naftopidil's impact on benign prostate hyperplasia (BPH) in a rat model and human patients.
Main Methods:
- Cell proliferation assays (WST-1) were used to test naftopidil's effect on prostate cells.
- Real-time RT-PCR quantified alpha(1)-AR subtype mRNA in a BPH rat model.
- Naftopidil was administered to BPH rats and patients to measure proliferative and apoptotic indexes.
Main Results:
- Naftopidil dose-dependently inhibited proliferation in cell lines expressing alpha(1d)-AR mRNA.
- Alpha(1d)-AR expression was significantly higher in the BPH rat model prostate compared to normal prostate.
- Naftopidil reduced cell proliferation without inducing apoptosis in both the rat model and BPH patients.
Conclusions:
- Alpha(1d)-AR plays a significant role in regulating prostate cellular proliferation.
- Blocking alpha(1d)-AR with naftopidil may inhibit prostate growth in BPH patients.
- Naftopidil treatment could potentially improve lower urinary tract symptoms and reduce prostate growth.
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