The Combined Inhibitory Effect of Terazosin and Finasteride on the Growth of DU145 Prostate Cancer Cells

Terazosin及Finasteride對DU145前列腺癌細胞生長之合併抑制效果

于大雄(Dah-Shyong Yu)

《臺灣泌尿科醫學會雜誌》 16卷4期 (2005/12) Pp. 137-145

摘要

研究目的：α1腎上腺接受體阻斷劑加上5-α-還原酶抑制劑在理論上可達到前列腺內細胞生長之抑制效果。此研究乃設計為探討結合finasteride與α1腎上腺接受體阻斷劑terazosin對前列腺癌之治療效果。
材料與方法：一人類前列腺癌細胞株DU145被用以測試finasteride與terazosin合併之效果。個別試劑之細胞毒性及細胞之感受性是以MTT方法比較。癌細胞外觀之變化是在倒立顯微鏡下觀察之。細胞週期變化是以Propidium iodide染色及染色體流式細胞分析儀測定，而細胞凋亡之變化是利用Annexin-V染色分析。
結果：Terazosin及finasteride二者都對DU145癌細胞有毒殺作用。DU145癌細胞對finasteride較terazosin治療更有感受性。而且其合併使用時表現出加乘之細胞毒殺能力。外觀上自從terazosin及finasteride治療後12小時細胞生長開始出現抑制萎縮及聚高情形，而且腫瘤細胞生長變得遲緩。在terazosin與terazosin/finasteride合併治療時可發現細胞之合成期比(SPF)逐漸降低，而G0/G1期細胞增強。相反的，單獨以finasteride治療之DU145癌細胞出現合成期比增加而G0/G1期減少之現象。細胞凋亡現象在terazosin治療後24小時增加，而在合併治療組則可在第六個小時出現。
結論：以上結果顯示利用腎上腺接受體阻斷劑及finasteride合併治療前列腺癌是可行的。針對某些臨床患有侵犯性前列腺癌之病人此類治療應該有其益處。

關鍵字

terazosin ； finasteride ； 細胞凋亡 ； 前列腺癌

並列摘要

OBJECTIVE: The addition of the α1-adrenoceptor blocker to a 5-α-reductase inhibitor has the theoretical advantage of providing more-complete blockade of intraprostatic cellular growth. This study was designed to elucidate the therapeutic efficacy of the combination of finasteride and the α1-adrenoceptor blocker, terazosin, for treatment of prostate cancer.
MATERIALS AND METHODS: A human PCa cell line, DU145, was tested using a combination of finasteride and terazosin. The cytotoxicity of the individual reagents and the cellular sensitivity were compared using the MTT method. Morphological changes in cancer cells were observed under phase-contrast microscopy. Changes in the cellular cycle were measured by propidium iodide staining and DNA flow cytometry, and variations in apoptosis were detected using Annexin-V staining.
RESULTS: Both terazosin and finasteride had cytostatic effects on DU145 tumor cells. The DU145 tumor cells were more sensitive to finasteride than terazosin treatment, and their combination exhibited synergistic cytotoxicity. Grossly, inhibition of tumor cell growth began from 12 hours with shrinkage and pile-ups, and retardation of the growth rate of tumor cells was observed after terazosin and finasteride treatment. A gradual decrease in S-phase-fraction (SPF) cells with an increase in G0/G1-phase cells was seen in both the terazosin and terazosin/finasteride combination treatment groups. On the contrary, DU145 tumor cells treated by finasteride alone demonstrated an increase in S-phase cells with a decrease in the G0/G1 population. Increased apoptotic cells were observed 24 hours after terazosin treatment which appeared earlier at 6 hours in the combined treatment group.
CONCLUSIONS: These results suggest that the combined treatment of prostate cancer using an α-adrenergic blocker and finasteride is feasible and should be advantageous in some clinical patients with advanced prostate cancer.

並列關鍵字

terazosin ； finasteride ； apoptosis ； prostate cancer