α1-adrenoceptor antagonists terazosin and doxazosin induce prostate apoptosis without affecting cell proliferation in patients with benign prostatic hyperplasia
α1-adrenoceptor antagonists terazosin and doxazosin induce prostate apoptosis without affecting cell proliferation in patients with benign prostatic hyperplasia
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DOI：
10.1016/s0022-5347(05)68873-8
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发表时间：
1999-06-01
影响因子：
6.6
通讯作者：
Kyprianou, N
中科院分区：
文献类型：
--
作者：
Chon, JK;Borkowski, A;Kyprianou, N
目的：最近有证据表明，α(1)阻滞剂doxazosin可诱导良性前列腺增生（BPH）患者的前列腺凋亡。(1)在本研究中，为了确定这种凋亡反应是由α(1)肾上腺素受体依赖机制介导的，还是仅针对doxazosin，我们检测了除doxazosin外，另一种α(1)阻滞剂terazosin对前列腺细胞生长动力学的影响。材料和方法：观察BPH患者、未治疗组（对照组）（n = 31）和接受特拉唑嗪（n = 42）和多沙唑嗪（n = 61）治疗的男性患者的细胞增殖和凋亡情况。特拉唑嗪（1至10毫克/天）和多沙唑嗪（2至8毫克/天）的治疗从1周到3年不等。采用Ki-67免疫染色法和TUNEL法分别评价前列腺组织（活检和前列腺切除术）上皮和基质成分的增殖和凋亡指标。根据平滑肌α -肌动蛋白免疫反应性确定前列腺基质的平滑肌细胞含量。结果：与未治疗的对照组相比，在terazosin和doxazosin治疗的第一个月内，前列腺上皮细胞和基质细胞均观察到明显的细胞凋亡诱导
Purpose: Recent evidence indicated that an alpha(1) blocker, doxazosin, induces prostate apoptosis in patients with benign prostatic hyperplasia (BPH).(1) In this study, to determine whether this apoptotic response was mediated by alpha(1) adrenoceptor-dependent mechanism or was specific to doxazosin, we examined the effect of another alpha(1) blocker, terazosin, in addition to doxazosin, on the dynamics of prostate cell growth.Materials and Methods: Cell proliferation and apoptosis were evaluated in BPH patients, an untreated (control) group (n = 31), and men treated with terazosin (n = 42) and doxazosin (n = 61) for the relief of the obstructive symptoms. Terazosin (1 to 10 mg./day) and doxazosin (2 to 8 mg./day) treatment varied from 1 week to 3 years. Ki-67 immunostaining and the TUNEL assay were used to evaluate the proliferative and apoptotic indices, respectively, in both the epithelial and stromal components of prostate (biopsy and prostatectomy) specimens. The smooth muscle cell content of the prostatic stroma was identified on the basis of smooth muscle alpha-actin immunoreactivity.Results: A significant induction of apoptosis was observed in both the prostatic epithelial and stromal cells within the first month of terazosin and doxazosin therapy, as compared with untreated controls (p