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特拉唑嗪体外诱导PC-3细胞凋亡的实验研究

Inducting apoptosis of Human prostatic cancer cell in vitro by α 1-adrenoceptor antagonists terazosin
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摘要 目的 :探讨特拉唑嗪诱导前列腺癌细胞株PC 3凋亡的作用。方法 :以不同浓度的特拉唑嗪体外作用于雄激素非依赖性前列腺癌PC 3细胞 ,细胞的生长抑制效应采用MTT检验。细胞凋亡指数采用双免疫荧光染色 (AnnexinV/PI)和流式细胞仪技术 ,凋亡细胞的形态学研究采用AO/EB双染色和激光共聚焦显微镜技术。结果 :经特拉唑嗪作用后的前列腺癌细胞通过诱导凋亡而被抑制了细胞的活性 ,这结果与药物浓度呈正相关 (r=0 .998,P <0 .0 5 )。细胞被阻滞于G0 ~G1期。结论 :特拉唑嗪通过诱导凋亡而抑制前列腺肿瘤的生长 ,具有治疗前列腺癌潜在的功能。 Objective:To investigate the effect of terazosin on human prostate cancer cell (PC-3 cell) combined use of flow cytometry(FCM) and confocal laser scanning microscopy(CLSM).Methods:Androgen independent PC-3 prostate cancer cells were used as an in vitro model. Cells were treated with varied concentrations of terazosin. The cytostatic effect of terazosin on PC-3 cells was determined by MTT, The apoptotic index of terazosin on PC-3 cells were assessed by two-color immunofluorescent staining (Annexin V/PI) and FCM. Apoptotic cell morphology was assessed by CLSM after AO/EB staining. Results:Our results indicate that treatment of prostate cancer cells with terazosin results in a significant loss of cell viability, via induction of apoptosis in a dose-dependent manner. Terazosin effectively blocked tumor cell growth and arrested cells in the G 0~G 1 phase of the cell cycle.Conclusions:These findings demonstrate the ability of terazosin to suppress prostate cancer cell growth in vitro by inducing apoptosis. This molecular basis of an alpha1-adrenoceptor independent action against prostate cancer cells by the quinazolines may have potential therapeutic significance in prostate cancer. The CLSM can clearly demonstrate the occurrence of apoptosis, and provide much more reliable information for the early apoptosis.
出处 《临床泌尿外科杂志》 2004年第11期678-679,682,共3页 Journal of Clinical Urology
关键词 前列腺肿瘤 特拉唑嗪 细胞凋亡 Prostatic neoplasms Terazosin Apoptosis
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参考文献6

  • 1Keledjian K, Kyprianou N. Anoikis induction by quinazoline based alpha 1-adrenoceptor antagonists in prostate cancer cells: antagonistic effect of bcl-2. J Urol, 2003, 169: 1150-1156.
  • 2彭黎明,王曾礼,主编. 细胞凋亡的基础与临床. 北京:人民卫生出版社,2000. 484-484.
  • 3Keledjian K, Borkowski A, Kim G,et al. Reduction of human prostate tumor vascularity by the alpha1-adrenoceptor antagonist terazosin. Prostate,2001,48:71-78.
  • 4Kyprianou N, Benning C M. Suppression of human prostate cancer cell growth by alpha1-adrenoceptor antagonists doxazosin and terazosin via induction of apoptosis. Cancer Res, 2000,60:4550-4555.
  • 5Cuellar D C, Rhee J, Kyprianou N. Alpha1-adrenoceptor antagonists radiosensitize prostate cancer cells via apoptosis induction. Anticancer Res,2002,22:1673-1679.
  • 6Benning C M, Kyprianou N. Quinazoline-derived alpha1-adrenoceptor antagonists induce prostate cancer cell apoptosis via an alpha1-adrenoceptor-independent action. Cancer Res,2002,62 :597-602.

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