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目的探讨多沙唑嗪(doxazosin)对雄激素非依赖性人前列腺癌PC-3细胞株增殖与凋亡的影响及其机制。方法用MTT法测定不同浓度多沙唑嗪对PC-3细胞生长抑制情况,用荧光显微镜、流式细胞仪观察多沙唑嗪对细胞凋亡的诱导作用,Western-Blot检测caspase-3,caspase-8,caspase-9、FADD和Bid、Bax、Bcl-2的表达水平。流式细胞仪检测不同时段Caspase-9抑制剂对细胞凋亡率的影响。结果多沙唑嗪可显著抑制PC-3细胞的体外生长,其25,50,100μmol/L浓度组的A值与对照组比较差异有统计学意义(P<0.01)。PC-3细胞中FADD、caspase-3,-9,-8和Bid、Bax表达显著增加,Bcl-2无明显变化。PC-3细胞凋亡可显著被caspase-9抑制剂抑制。结论多沙唑嗪能诱导PC-3细胞凋亡,其作用可能通过死亡信号途径激活caspase-8,同时Bid,Bax表达上调,引发线粒体途径激活caspase-9和caspase-3而实现的。
Objective To investigate the effect and mechanism of doxazosin on proliferation and apoptosis of androgen-independent human prostate cancer cell line PC-3. Methods The inhibitory effects of doxazosin on the growth of PC-3 cells were determined by MTT assay. The apoptosis induced by doxazosin was observed by fluorescence microscopy and flow cytometry. The expressions of caspase-3, caspase-3 -8, caspase-9, FADD and Bid, Bax, Bcl-2 expression levels. The effect of Caspase-9 inhibitor on the apoptosis rate was detected by flow cytometry at different time points. Results Doxazosin significantly inhibited the growth of PC-3 cells in vitro. The A values in 25, 50 and 100 μmol / L groups were significantly different from those in control group (P <0.01). The expression of FADD, caspase-3, -9, -8 and Bid, Bax in PC-3 cells increased significantly, but there was no significant change in Bcl-2. PC-3 cell apoptosis can be significantly inhibited by a caspase-9 inhibitor. CONCLUSION Doxazosin can induce the apoptosis of PC-3 cells, which may activate caspase-8 through the death signal pathway, up-regulate the expression of Bid and Bax, and trigger the activation of caspase-9 and caspase-3 by mitochondrial pathway.