Antagonism of estrogen-mediated cell proliferation by raloxifene in prevention of ageing-related prostatic hyperplasia.
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 alpha-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. Furthermore, 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.
Yang
Rui
R
Bioactive Materials Key Lab of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Ma
Yu-Xia
YX
Chen
Lin-Feng
LF
Zhou
Ying
Y
Yang
Zhan-Po
ZP
Zhu
Yan
Y
Du
Xiao-Ling
XL
Shi
Jian-Dang
JD
Ma
Hong-Shun
HS
Zhang
Ju
J
D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use; D000375:Aging; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D018120:Finasteride / Q000627:therapeutic use; D006801:Humans; D008297:Male; D023421:Models, Animal; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011467:Prostate / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000517:prevention & control*; D020849:Raloxifene Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use
D058891:5-alpha Reductase Inhibitors; D004965:Estrogen Antagonists; D018809:Proliferating Cell Nuclear Antigen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride; D018120:Finasteride
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