米非司酮对雄激素非依赖性前列腺癌LNCaPC_(4-2)和PC3细胞的作用机制

Inhibiting Mechanism of Mifepristone on Androgen-Independent Prostate Cancer Cell Lines LNCaPC_(4-2) ,PC3 in Vitro

为探讨抗孕激素药米非司酮对雄激素非依赖性前列腺癌细胞株LNCaPC4 2 、PC3的促凋亡及生长抑制作用 ,将不同浓度的米非司酮加入到体外培养的 2株前列腺癌细胞中 ,分别在培养后 3d、5d、7d用SRB染色法检测细胞生长抑制率 ;用流式细胞仪检测加药后 2 4h、48hLNCaPC4 2 和PC3细胞凋亡情况。发现 :高浓度米非司酮 ( 2 0μmol/L)对雄激素非依赖性细胞株LNCaPC4 2 、PC3于 3d、5d、7d的细胞生长抑制率分别为 5 5 .79%、66.3 7%、71 .5 4%和 87.42 %、98.1 5 %、1 0 0 %。不同浓度米非司酮即 2 .5、5、1 0、1 5、2 0 μmol/L对LNCaPC4 2 、PC3细胞株 7d时的细胞生长抑制率分别为 1 7.0 7%、3 5 .77%、5 3 .66%、63 .41 %、71 .5 4%和 48.2 5 %、63 .42 %、82 .3 7%、95 .3 1 %、1 0 0 %。前列腺癌细胞株LNCaPC4 2 受 1 5 μmol/L米非司酮作用 2 4h和 48h细胞凋亡率分别为 1 9.3 0 %、3 0 .0 4% ;PC3受米非司酮 1 5 μmol/L作用 2 4h细胞凋亡率为 44.5 2 %。提示 :米非司酮对LNCaPC4 2 、PC3细胞株有时间和剂量依赖的生长抑制作用 ,其生长抑制作用是通过促进细胞凋亡实现的。

The aim was to present our attempts on investigating the pro-apoptosis and growth suppression effects of antiprogestin mifepristone on androgen-independent prostate cancer cell lines LNCaPC 4-2 , PC3 in vitro. Using SRB method, the inhibition rates of different concentrations of mifepristone on the two cell lines were studied after drug 3 d, 5 d and 7 d after administration. The study also assessed the apoptosis rates induced by 15 μmol/L mifepristone on LNCaPC 4-2 , PC3 cell lines after 24 h, 48 h treatment. When the LNCaPC 4-2 cell line and the PC3 cell line were treated with 20 μmol/L mifepristone, the corresponding rates were 55.79%, 66.37%, 71.54% and 87.42%, 98.15 %, 100% on the 3 rd day, 5 th day and 7 th day. When the two cell lines were dealt with different concentrations of mifepristone 2.5 μmol/L, 5 μmol/L, 10 μmol/L, 15 μmol/L, 20 μmol/L, the corresponding suppression rates on the 7 th day were: 17.07%, 35.77%, 53.66%, 63.41%, 71.54 % and 48.25%, 63.42%, 82.37%, 95.31 %, 100% respectively. Using flow cytometry method, the apoptosis rates of 15 μmol/L mifepristone for LNCaPC 4-2 cell line were: 19.30% at 24 h and 30.04 % at 48 h, for PC3 cell line was 44.52% at 24 h. Antiprogestin mifepristone can induce apoptosis of androgen-independent prostate cancer cell lines LNCaPC 4-2 , PC3 in vitro. This pro-apoptosis effect is time-and-dose dependent.