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 s...

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Veröffentlicht in:The Prostate 2009-10, Vol.69 (14), p.1521-1528
Hauptverfasser: Kojima, Yoshiyuki, Sasaki, Shoichi, Oda, Nobuyuki, Koshimizu, Taka-Aki, Hayashi, Yutaro, Kiniwa, Mamoru, Tsujimoto, Gozoh, Kohri, Kenjiro
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container_end_page 1528
container_issue 14
container_start_page 1521
container_title The Prostate
container_volume 69
creator Kojima, Yoshiyuki
Sasaki, Shoichi
Oda, Nobuyuki
Koshimizu, Taka-Aki
Hayashi, Yutaro
Kiniwa, Mamoru
Tsujimoto, Gozoh
Kohri, Kenjiro
description 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 
doi_str_mv 10.1002/pros.21003
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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 &lt; 0.001). Naftopidil administration inhibited cell proliferation without apoptosis in the BPH model rat and BPH patients. CONCLUSIONS α1d‐AR may play an important role in the regulation of cellular proliferation in the prostate, and α1d‐AR blockage by naftopidil may not only improve lower urinary tract symptoms but also inhibit prostate growth in BPH patients. Prostate 69: 1521–1528, 2009. © 2009 Wiley‐Liss, Inc.</description><identifier>ISSN: 0270-4137</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.21003</identifier><identifier>CODEN: PRSTDS</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>alpha1-adrenoceptor subtype ; alpha1-blocker ; benign prostatic hyperplasia ; Biological and medical sciences ; cell proliferation ; Gynecology. Andrology. Obstetrics ; Male genital diseases ; Medical sciences ; Nephrology. Urinary tract diseases ; prostate growth ; Tumors ; Tumors of the urinary system ; Urinary tract. 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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 &lt; 0.001). Naftopidil administration inhibited cell proliferation without apoptosis in the BPH model rat and BPH patients. CONCLUSIONS α1d‐AR may play an important role in the regulation of cellular proliferation in the prostate, and α1d‐AR blockage by naftopidil may not only improve lower urinary tract symptoms but also inhibit prostate growth in BPH patients. Prostate 69: 1521–1528, 2009. © 2009 Wiley‐Liss, Inc.</description><subject>alpha1-adrenoceptor subtype</subject><subject>alpha1-blocker</subject><subject>benign prostatic hyperplasia</subject><subject>Biological and medical sciences</subject><subject>cell proliferation</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Male genital diseases</subject><subject>Medical sciences</subject><subject>Nephrology. Urinary tract diseases</subject><subject>prostate growth</subject><subject>Tumors</subject><subject>Tumors of the urinary system</subject><subject>Urinary tract. 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Andrology. Obstetrics</topic><topic>Male genital diseases</topic><topic>Medical sciences</topic><topic>Nephrology. Urinary tract diseases</topic><topic>prostate growth</topic><topic>Tumors</topic><topic>Tumors of the urinary system</topic><topic>Urinary tract. Prostate gland</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kojima, Yoshiyuki</creatorcontrib><creatorcontrib>Sasaki, Shoichi</creatorcontrib><creatorcontrib>Oda, Nobuyuki</creatorcontrib><creatorcontrib>Koshimizu, Taka-Aki</creatorcontrib><creatorcontrib>Hayashi, Yutaro</creatorcontrib><creatorcontrib>Kiniwa, Mamoru</creatorcontrib><creatorcontrib>Tsujimoto, Gozoh</creatorcontrib><creatorcontrib>Kohri, Kenjiro</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kojima, Yoshiyuki</au><au>Sasaki, Shoichi</au><au>Oda, Nobuyuki</au><au>Koshimizu, Taka-Aki</au><au>Hayashi, Yutaro</au><au>Kiniwa, Mamoru</au><au>Tsujimoto, Gozoh</au><au>Kohri, Kenjiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prostate growth inhibition by subtype-selective alpha1-adrenoceptor antagonist naftopidil in benign prostatic hyperplasia</atitle><jtitle>The Prostate</jtitle><addtitle>Prostate</addtitle><date>2009-10-01</date><risdate>2009</risdate><volume>69</volume><issue>14</issue><spage>1521</spage><epage>1528</epage><pages>1521-1528</pages><issn>0270-4137</issn><eissn>1097-0045</eissn><coden>PRSTDS</coden><abstract>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 &lt; 0.001). Naftopidil administration inhibited cell proliferation without apoptosis in the BPH model rat and BPH patients. CONCLUSIONS α1d‐AR may play an important role in the regulation of cellular proliferation in the prostate, and α1d‐AR blockage by naftopidil may not only improve lower urinary tract symptoms but also inhibit prostate growth in BPH patients. Prostate 69: 1521–1528, 2009. © 2009 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><doi>10.1002/pros.21003</doi><tpages>8</tpages></addata></record>
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subjects alpha1-adrenoceptor subtype
alpha1-blocker
benign prostatic hyperplasia
Biological and medical sciences
cell proliferation
Gynecology. Andrology. Obstetrics
Male genital diseases
Medical sciences
Nephrology. Urinary tract diseases
prostate growth
Tumors
Tumors of the urinary system
Urinary tract. Prostate gland
title Prostate growth inhibition by subtype-selective alpha1-adrenoceptor antagonist naftopidil in benign prostatic hyperplasia
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