中文摘要：

目的探讨沙利度胺联合干扰素（IFN）对急性髓系白血病细胞系Kasumi-1细胞的增殖抑制作用及其机制。方法沙利度胺、IFN以及两药联合处理Kasumi．1细胞，采用CCK．8法检测细胞增殖抑制率，流式细胞术检测细胞凋亡率，ELISA法检测细胞培养上清血管内皮生长因子（VEGF）水平，Westemblot法检测凋亡相关蛋白的表达。结果在50～500μg／ml范围内沙利度胺可抑制Kasumi-1细胞增殖，并呈浓度依赖性[24h的IC59值为（451．13±6．92）pg／ml、48h的IC50值为（362．50±14．52）pg／ml]；在500～5000U／ml范围内，IFN浓度依赖性地抑制Kasumi-1细胞增殖[24h的IC50值为（2209±127）U／ml、48h的IC50值为（1393±63）U／ml]。350gg／ml沙利度胺和1400U／mlIFN作用48h，Kasumi．1细胞的凋亡率分别为（14．68±2．61）％和（21．71±0．71）％，与对照组[（0．89±0．38）％]相比，差异有统计学意义（P值均〈0．01）；两药联合作用后Kasumi．1细胞的增殖抑制率为（88．50±2．40）％，凋亡率为（41．95±3．41）％，与对照组和各单药组比较，差异均有统计学意义（P值均〈0．01）。沙利度胺、IFN单药及两药联合组VEGF水平分别为（141．11±3．70）、（119．90±2．00）和（94．61±5．46）ng／L，两药联合组明显低于单药组（P值均〈0．05）。沙利度胺、IFN单药作用Kasumi-1细胞48h能不同程度下调Bcl-2的表达，上调p-P38（同时P38表达量下降）、Bax、细胞色素C、活化型（cleaved）Caspase-3、8、9的表达，与对照组比较差异均有统计学意义（P值均〈0．05）；沙利度胺联合IFN该作用进一步加强（P值均〈0．05）。结论沙利度胺和IFN可协同抑制Kasumi-1细胞增殖、诱导其凋亡，其可能是通过线粒体和死亡受体途径，并活化P38信号通路诱导细胞凋亡和抑制Kasumi-1细胞VEGF的自分泌来实现。

英文摘要：

Objective To explore the inhibitory effect of thalidomide combined with interferon （IFN） on the human acute myeloid leukemia cell line Kasumi-1 and its mechanism. Methods The inhibitiory effect of Kasumi- 1 cells by thalidomide, interferon or combination was detected by CCK- 8 method, the apoptosis by flow cytometry, the expression of apoptosis related proteins by Western blot, vascular endothelial growth factor （VEGF） concentration in culture supematant by ELISA. Results Thalidomide inhibited the proliferation of Kasumi-1 in a dose-dependent manner from 50 μg/ml to 500 μg/ml with an ICso of （451.13 ± 6.92） μg/ml at 24 h and （362.50 ±14.52） μg/ml at 48 h. IFN also demonstrated the inhibitory capacity in a dose-dependent manner from 500 U/ml to 5 000 U/ml, with an IC50 of（2 209±127）U/ml at 24 h and （ 1 393±63 ）U/ml at 48 h. The apoptosis rates of Kasumi-1 cells treated with thalidomide 350 gg/ml or IFN 1 400 U/ml for 48 h were （14.68±2.61）% and （21.71±0.71）%, respectively, significantly higher than control group （P〈0.01）. In combination group the inhibition and the apoptosis rate were （88.50±2.40）% and （41.95±3.41）%, significantly higher than control and each single agent group （P〈0.01）. The VEGF concentrations of combination group [ （94.61±5.46） ng/L] decreased significantly, as compared to thalidomide group [ （141.11±3.70） ng/L] and IFN group [ （119.90±2.00） ng/L ] （P 〈 0.05 ）. Western blot analysis showed Bcl-2 expression of Kasumi-1 cells decreased, while p-P38, Bax, cytochrome C, cleaved-Caspase-3, 8, 9 increased after treated with thalidomide 350 μg/ml or IFN 1 400 U/ml for 48 h. When treated with the combination agents, the expression of Bcl-2 further decreased and p-P38, Bax, cytochrome C, cleaved-Caspase-3, 8, 9 further increased as compared with each single agent （P 〈 0.05）. Conclusions Thalidomide and IFN could synergistically inhibit the proliferation of Kasumi- 1 cells probably through inducing apoptosis via th