[Effects of 4-hydroxytamoxifen on prostate smooth muscle cells: an in vitro experiment]
Yi-Ming Fu1, Qiu-Ming Li, Shao-Bin Ni
1Department of Urology, First Hospital of Harbin Medical University, Harbin 150001, China.
Objective:
To investigate the effects of 4- hydroxytamoxifen (OHT) on the proliferation and apoptosis of prostate smooth muscle cells and the expression of estrogen receptor (ER) and androgen receptor (AR).
Methods:
Prostate smooth muscle cells were isolated from the resected specimens of prostate glands of 10 patients with benign prostatic hypertrophy (BPH), cultured, and exposed to estradiol (E(2)), diethylstilbestrol (DES), and OHT of different concentrations (1 x 10(-8) - 1 x 10(-5) mol/L) or mixture of E(2) (1 x 10(-8) - 1 x 10(-6) mol/L) with OHT (1 x 10(-7) mol/L). Flow cytometry was used to test the proliferation and apoptosis of the cells, and immunocytochemistry was used to test the expression of estrogen and androgen receptors.
Results:
E(2) and DES promoted the proliferation of the prostate smooth muscle cells in a certain concentration range, but not dose-dependently, and OHT at the concentration of 1 x 10(-8) mol/L slightly increased the G(2)-M peak rate of the prostate smooth muscle cells, but suppressed the G(2)-M peak rate dose-dependently when its concentration was >or= 1 x 10(-7) mol/L (P < 0.05) and this suppression effect was dose-dependently (r = -0.312, P = 0.011). E(2) at the concentration >or= 1 x 10(-5) mol/L and DES at the concentration >or= 1 x 10(-6) mol/L slightly promoted the apoptosis of the prostate smooth muscle cells, but not dose-dependently, and OHT at the concentrations from 1 x 10(-8) mol/L to 1 x 10(-5) mol/L promoted the apoptosis of the prostate smooth muscle cells dose-dependently (r = 0.363, P = 0.021) and this effect could not be reversed by administration of E(2) at the concentration 1 x 10(-8) - 1 x 10(-6) mol/L (P > 0.05). E(2), DES, and OHT of different concentrations all increased the ERalpha and AR positive staining rates of the prostate smooth muscle cells (all P < 0.05).
Conclusions:
OHT suppresses the proliferation and promotes the apoptosis of prostate smooth muscle cells, and these functions do not depend on the estrogen receptor pathway. Low blood OHT concentration after oral administration of TAM and up-regulation of estrogen receptors by OHT may be the caused of the inefficiency of TAM for treatment of BPH.
Insights
4-hydroxytamoxifen (OHT) inhibits prostate smooth muscle cell proliferation and promotes apoptosis, independent of estrogen receptor pathways. This suggests OHT
Area of Science:
- Cell Biology
- Endocrinology
- Urology
Background:
- Benign prostatic hyperplasia (BPH) involves prostate smooth muscle cell proliferation.
- Estrogen and androgen receptors play roles in prostate tissue.
- Tamoxifen derivatives are used in hormone-related therapies.
Purpose of the Study:
- To investigate the effects of 4-hydroxytamoxifen (OHT) on prostate smooth muscle cell proliferation and apoptosis.
- To examine the impact of OHT on estrogen receptor (ER) and androgen receptor (AR) expression in these cells.
Main Methods:
- Prostate smooth muscle cells were isolated from BPH patient specimens.
- Cells were cultured and treated with estradiol (E2), diethylstilbestrol (DES), and OHT at various concentrations.
- Flow cytometry assessed cell proliferation and apoptosis; immunocytochemistry evaluated ER and AR expression.
Main Results:
- OHT suppressed prostate smooth muscle cell proliferation dose-dependently.
- OHT promoted prostate smooth muscle cell apoptosis dose-dependently, an effect not reversed by E2.
- E2, DES, and OHT increased ERalpha and AR positive staining rates in the cells.
Conclusions:
- OHT inhibits prostate smooth muscle cell proliferation and induces apoptosis, independent of the estrogen receptor pathway.
- Potential reasons for tamoxifen's inefficiency in BPH treatment may include low OHT blood concentration and OHT-induced ER upregulation.
