地西他滨对MDS-L细胞增殖的抑制作用及其相关作用机制研究

发布时间：2018-05-26 23:15

  本文选题：骨髓增生异常综合征 + 地西他滨　； 参考：《中国实验血液学杂志》2017年05期

【摘要】：目的:探讨去甲基化药物地西他滨(Decitabine,DAC)的不同剂量对MDS-RAEB(骨髓增生异常综合征-原始细胞增多型)细胞株MDS-L细胞增殖的抑制作用及其相关作用机制。方法:采用LC-MS/MS生物分析法检测应用DAC 20和15 mg/m~2×5 d的两组MDS患者血药浓度水平;模拟患者的血药浓度,设计不同剂量的DAC(0.5、0.3、0.2、0.1、0.05、0.025和0.01μg/ml)作用于MDS-L细胞24、48、72和96 h,用CCK-8法检测细胞的增殖抑制效应;光学显微镜下观察细胞形态学变化;流式细胞术检测细胞周期变化及凋亡情况;PCR检测DAC作用后MDS-L细胞P15的甲基化水平的变化。结果:注射结束即刻,DAC 20 mg/m~2×5 d组患者血药浓度为174.08±80.15(84.7-311)ng/ml,明显高于15 mg/m~2×5 d组的89.87±32.94(43.2-165)ng/ml(P=0.014)。DAC对MDS-L细胞有明显增殖抑制作用,且呈时间浓度依赖关系(r=0.786),但DAC≥0.1μg/ml浓度时,各浓度对细胞的抑制作用无明显差异。DAC处理后G_1期细胞明显增多,而S期细胞明显减少。与对照组相比,MDS-L细胞经DAC 0.01、0.025、0.05、0.1、0.2μg/ml作用96 h后,P15INK4B表达均下降,但各浓度之间无显著差异(P0.05)。结论:低浓度DAC对MDS-L细胞有明显增殖抑制作用,在0.1和0.2μg/ml浓度时,对MDS-L细胞的抑制作用达理想范围。DAC可以将MDS-L细胞阻滞在G_1期,阻止G_1期细胞向S期细胞转化。
[Abstract]:Aim: to investigate the inhibitory effects of different doses of the demethylated drug Decitabine DACon on the proliferation of MDS-RAEBcell line MDS-L cells and its related mechanism. Methods: LC-MS/MS bioassay was used to detect the serum drug concentration of MDS patients who were treated with DAC 20 and 15 mg/m~2 脳 5 d. MDS-L cells were treated with different doses of Dacron (0.5g / ml, 0.3g / ml and 0.025 渭 g / ml) for 2448g / ml for 72 h and 96 h, respectively. The proliferation inhibition effect was detected by CCK-8 assay, and the morphological changes were observed under optical microscope. The changes of cell cycle and apoptosis were detected by flow cytometry. The methylation level of P15 in MDS-L cells was detected by DAC. Results: the plasma drug concentration was 174.08 卤80.15 渭 g/ml 84.7-311ng / ml in the 20 mg/m~2 脳 5 d group, which was significantly higher than that in the 15 mg/m~2 脳 5 d group (89.87 卤32.94(43.2-165)ng/ml(P=0.014).DAC), in a time-dependent manner, but when DAC 鈮，

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