Ng A Y, Bales W, Veltri R W
UroCor, Inc., Oklahoma City, Oklahoma 73104, USA.
Anal Quant Cytol Histol. 2000 Feb;22(1):45-54.
To assess the mechanisms of action of phenylbutyrate (PB), an investigational chemotherapeutic agent for prostate cancer (PCa), in apoptosis induction in PCa cell lines in vitro.
We analyzed the differential expression of different apoptosis modulators, Bcl-2, Bax, p53 and Fas, for their potential role in PB-induced apoptosis using relative quantitative flow cytometry (FCM). Both androgen-dependent (LNCaP) and androgen-independent (C-4-2, PC-3-PF and DU145) human PCa cell lines were examined.
PB induced apoptosis in PCa cell lines in a dose-dependent manner. Fifty percent apoptosis could be induced by 5-10 mM PB. Bcl-2 was down-regulated 30-75% and the Bax:Bcl-2 ratio elevated in apoptotic PCa cell lines regardless of their androgen dependency or p53 status. FCM revealed a heterogeneous stimulatory effect on the expression of Bax and Bcl-2 in PC3-PF cells at 0.5-2.5 mM PB. In a p53-positive cell line (DU145), p53 was repressed by 70% and Fas elevated sixfold with 10 mM PB.
Our data show that PB-induced PCa apoptosis is associated with the relative repression of Bcl-2 and with up-regulation of Bax and Fas proteins and that this PB-induced apoptosis is independent of p53 and androgen-dependency status of PCa cell lines.
评估苯基丁酸盐（PB），一种用于前列腺癌（PCa）的试验性化疗药物，在体外诱导PCa细胞系凋亡中的作用机制。
我们使用相对定量流式细胞术（FCM）分析了不同凋亡调节因子Bcl-2、Bax、p53和Fas的差异表达，以探讨它们在PB诱导凋亡中的潜在作用。对雄激素依赖型（LNCaP）和雄激素非依赖型（C-4-2、PC-3-PF和DU145）人PCa细胞系均进行了检测。
PB以剂量依赖方式诱导PCa细胞系凋亡。5-10 mM PB可诱导50%的细胞凋亡。无论其雄激素依赖性或p53状态如何，凋亡的PCa细胞系中Bcl-2下调30%-75%，Bax:Bcl-2比值升高。FCM显示，在0.5-2.5 mM PB作用下，PC3-PF细胞中Bax和Bcl-2的表达受到异质性刺激。在p53阳性细胞系（DU145）中，10 mM PB可使p53表达降低70%，Fas表达升高6倍。
我们的数据表明，PB诱导的PCa凋亡与Bcl-2的相对抑制、Bax和Fas蛋白的上调有关，且这种PB诱导的凋亡与PCa细胞系的p53和雄激素依赖性状态无关。
