关键词: 多沙唑嗪, 特拉唑嗪 , α1肾上腺素受体, 前列腺肿瘤

Abstract: Objective: To investigate the biological action of α1-adrenoceptor antagonists against human androgen-independent prostate cancer cells and to explore its molecular mechanism. Methods: Passage cultures of DU145 cells were exposed to an increasing concentration（0.1，1，10，25，100μmol/L）of doxazosin, terazosin, tamsulosin, or naftopidil for 24，48，72 and 96h, and DU-145 cells not exposing to drugs were served as the control group. The number of viable cells was assessed using an MTT colotmetric. Cells were treated with drugs (25?μmol/L) for 48h, and cell cycles, apoptosis and morphological changes by means of flow cytometry, FACS analysis, and electron microscope technique, respectively. Expressions of apoptosis-related factors and proteins were also determined. Results: After 48h of treatment with doxazosin or terazosin at 25，100μmol/L, the cell viability of DU-145 prostate cancer cells were significantly different from that of the controls（P＜0.01）. Percentages of relative distribution in each phase of the cell cycle were similar to those of the controls. Either drugs resulted in a significant increase in the number of apoptotic cells, and a characteristic appearance of the apoptotic cell morphology was determined by electron microscopy. Immunohistochemical analysis revealed a moderate increased expression of both Fas and TGFβ1, whereas expression of bcl-2 was not significantly different from that of the controls. Tamsulosin and naftopidil had no effect on the prostate cancer cell viability. Conclusions: The quinazoline-derived α1-adrenoceptor antagonists, doxazosin and terazosin, activate apoptosis in prostate cancer cells without interfering with cell cycle progression, which provides a rationale for advancing either drugs as potential antitumor agents in the treatment of advanced prostate cancer.

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