地塞米松衍生物对K562细胞增殖的抑制作用及机制

The investigation of effect of dexamethasone derivative on the proliferation inhibition and its molecular mechanism of K562

目的:研究地塞米松衍生物对K562细胞的增殖抑制作用,并对其作用机制进行初步的探讨。方法:以地塞米松为原料合成并纯化得到新的衍生物。用不同浓度的地塞米松衍生物对K562细胞进行处理,通过MTT比色法检测细胞增殖抑制率,电镜法观察细胞凋亡的形态学变化,免疫细胞化学法测定细胞Bcl-2,Fas表达,比色法检测Caspase-3的活性变化。结果:地塞米松衍生物能抑制K562细胞的增殖,使Bcl-2表达降低,Fas表达上调,Caspase-3活性增强,诱导K562细胞凋亡。结论:地塞米松衍生物可能通过诱导K562细胞凋亡而抑制细胞增殖。其诱导细胞凋亡的机制可能与抑制Bcl-2蛋白的表达,上调Fas受体,进而激活细胞内的Caspase-3有关。

OBJECTIVE To investigate the effect of dexamethasone derivative on the growth of K562 cells and to study its molecular mechanism. METHODS New dexamethasone derivative was synthesized from dexamethasone. K562 cells were treated with different dosages of dexamethasone derivative. Cell inhibitory rate was determined by MTT, cell morphology variation was observed by electronmicroscope stain. Bcb2, Fas expression was detected by immunocytochemistry and Caspase-3 activity was detected by Colorimetric method. RESULTS Dexamethasone derivative could inhibit the proliferation of K562 cells,down - regulate Bcl 2 expression, upregulate Fas expression,activate Caspase-3 and induce K562 cells apoptosis. CONCLUSION Dexamethasone derivative may induce apoptosis to inhibit cell proliferation. The mechanism of dexamethasone derivative induced apoptosis in K562 cells may be related to downregulation of Bcl-2 expression, up-regulation of Fas expression,and activation of Caspase-3.