Naftopidil, a selective α-1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest
Naftopidil, a selective α-1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest
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DOI：
10.1002/ijc.23095
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发表时间：
2008-01-15
影响因子：
6.4
通讯作者：
Sugimura, Yoshiki
中科院分区：
文献类型：
--
作者：
Kanda, Hideki;Ishii, Kenichiro;Sugimura, Yoshiki
α-1 肾上腺素受体拮抗剂通常用于治疗伴有下尿路症状的良性前列腺增生。萘哌地尔是一种选择性 α-1 肾上腺素受体拮抗剂，在日本经常使用，因为它的副作用较少。在这里，我们首次证明萘哌地尔对雄激素敏感和不敏感的人前列腺癌细胞系具有生长抑制作用。在雄激素敏感的LNCaP细胞中引起癌细胞生长50％抑制(IC50)的浓度为22.2+/-4.0μM，在雄激素不敏感的PC-3细胞中为33.2+/-1.1μM。 FACS分析显示萘哌地尔对细胞生长的抑制是由于G1细胞周期的停滞。萘哌地尔处理的LNCaP细胞中p27(kip1)和p21(cip1)的表达显着增加。在PC-3细胞中，萘哌地尔诱导p21(cip1)，但不诱导p27(kip1)。在体内，与媒介物处理的对照相比，口服萘哌地尔给裸鼠抑制PC-3肿瘤的生长。这些结果表明萘哌地尔可能有助于前列腺癌的化学预防和激素难治性前列腺癌的干预。 (c) 2007 年 Wiley-Liss, Inc.
alpha-1 adrenoceptor antagonists are generally prescribed for benign prostate hyperplasia with lower urinary tract symptoms. Naftopidil, a selective a-1 adrenoceptor antagonist, is frequently used in Japan because it has fewer side effects. Here we demonstrate for the first time that naftopidil has growth inhibitory effect in androgen-sensitive and -insensitive human prostate cancer cell lines. The concentrations causing 50% inhibition (IC50) of cancer cell growth were 22.2 +/- 4.0 mu M in androgen -sensitive LNCaP cells and 33.2 +/- 1.1 mu M in androgen-insensitive PC-3 cells. FACS analysis revealed that cell growth inhibition by naftopidil was due to the arrest of the G1 cell cycle. Expressions of p27(kip1) and p21(cip1) were significantly increased in LNCaP cells treated with naftopidil. In PC-3 cells, naftopidil induced p21(cip1) but not p27(kip1) In vivo, oral administration of naftopidil to nude mice inhibited the growth of PC-3 tumors as compared to vehicle-treated controls. These results suggest that naftopidil may be useful in the chemoprevention of prostate cancer and the intervention of hormone refractory prostate cancer. (c) 2007 Wiley-Liss, Inc.