Antagonism of estrogen-mediated cell proliferation by raloxifene in prevention of ageing-related prostatic hyperplasia  

作　　者：Rui Yang Yu-Xia Ma Lin-Feng Chen Ying Zhou Zhan-Po Yang Yan Zhu Xiao-Ling Du Jian-Dang Shi Hong-Shun Ma Ju Zhang 

机构地区：[1]Bioactive Materials Key Lab of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Life Sciences, Nankai University, Tianjin 300071, China [2]Dana Farber Cancer Institute, Harvard Medical School Boston, MA 02445, USA [3]Department of Urology, Tianjin First Central Hospital, Tianjin 300192, China [4]Molecular Cardiology Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA

出　　处：《Asian Journal of Andrology》2010年第5期735-743,共9页亚洲男性学杂志（英文版）

基　　金：Acknowledgment This research was funded by the following grants： the National Basic Research Programs, China （973 Programs, No. 2009CB918904, No. 2010CB945003）, the National Natural Science Foundation of China （No. 30872592）, Joint Research Fund for Overseas Chinese Scholars and Scholars in Hong Kong and Macao, China （No. 30928027）, and the key research project of Tianjin Municipal Science and Technology Commission, China （No. 09ZCKFSF00800）.

摘　　要：Estrogen has important roles in the initiation and development of benign prostatic hyperplasia （BPH）. Regulators of the estrogen receptor （ER） are tissue- and cell-specific. We evaluated the effect of estrogen antagonist, raloxifene （Ral）, on the prevention and treatment of BPH by investigating its effect on the proliferation of two different prostate cell lines： a stromal cell line, WPMY-1, and a benign prostatic hyperplasia epithelial cell line, BPH-1. We additionally evaluated its effect on prostatic hyperplasia induced by estrogen and androgen in a rat model. The effect of Ral on the prevention of prostatic hyperplasia was analyzed by haematoxylin and eosin staining and quantitative immunohistochemistry （IHC） for proliferating cell nuclear antigen and α-smooth muscle actin. In vitro and in vivo, tamoxifen （Tam）, another anti-estrogen drug, and finasteride （Fin）, a drug for the clinical treatment of BPH, served as efficacy controls. The in vitro data showed that neither Ral nor Tam alone affected the proliferation of WPMY-1 and BPH-1, but both antagonized the effect of oestradiol in promoting the proliferation of the two cells. Results from the IHC staining of the rat prostates indicated that, similar to Tam and Fin, Ral inhibited the proliferation of stromal cells in vivo. Interestingly, in contrast to Tam, both Ral and Fin inhibited the proliferation of epithelial cells. Furthemore, Ral treatment much strongly decreased the number of prostatic acini and the surrounding layers of smooth muscle cells than Fin （P 〈 0.05）. Our data showed for the first time that Ral may have a role in the response of the rat prostate to selective ER modulators.Estrogen has important roles in the initiation and development of benign prostatic hyperplasia （BPH）. Regulators of the estrogen receptor （ER） are tissue- and cell-specific. We evaluated the effect of estrogen antagonist, raloxifene （Ral）, on the prevention and treatment of BPH by investigating its effect on the proliferation of two different prostate cell lines： a stromal cell line, WPMY-1, and a benign prostatic hyperplasia epithelial cell line, BPH-1. We additionally evaluated its effect on prostatic hyperplasia induced by estrogen and androgen in a rat model. The effect of Ral on the prevention of prostatic hyperplasia was analyzed by haematoxylin and eosin staining and quantitative immunohistochemistry （IHC） for proliferating cell nuclear antigen and α-smooth muscle actin. In vitro and in vivo, tamoxifen （Tam）, another anti-estrogen drug, and finasteride （Fin）, a drug for the clinical treatment of BPH, served as efficacy controls. The in vitro data showed that neither Ral nor Tam alone affected the proliferation of WPMY-1 and BPH-1, but both antagonized the effect of oestradiol in promoting the proliferation of the two cells. Results from the IHC staining of the rat prostates indicated that, similar to Tam and Fin, Ral inhibited the proliferation of stromal cells in vivo. Interestingly, in contrast to Tam, both Ral and Fin inhibited the proliferation of epithelial cells. Furthemore, Ral treatment much strongly decreased the number of prostatic acini and the surrounding layers of smooth muscle cells than Fin （P 〈 0.05）. Our data showed for the first time that Ral may have a role in the response of the rat prostate to selective ER modulators.

关 键 词：ESTROGEN prostatic hyperplasia RALOXIFENE rats 

分 类 号：Q579.13[生物学—生物化学] TQ463[化学工程—制药化工]