脂多糖与干扰素α联用诱导白血病U937细胞凋亡及其机制

The Synergy Effects of Lipopolysaccharide and Interferon-Alpha on Apoptosis of U937 Leukemia Cells

目的:探讨Toll样受体配体内毒素脂多糖(LPS)与干扰素(IFN)-α联用对白血病U937细胞凋亡的作用及其对caspase-8基因表达的影响。方法:将200μg/L的LPS和(或)2000U/mL的IFN-α作用于U937细胞,MTT检测细胞生长抑制率,流式细胞术(FCM)检测细胞凋亡率,半定量逆转录-聚合酶链反应(RT-PCR)法检测作用48h后U937细胞中caspase-8mRNA的表达。结果:LPS与IFN-α联用较单用LPS、IFN-α能明显抑制U937细胞增殖、增加细胞凋亡率(P<0.01),且各药物组较对照组比较差异均有统计学意义(P<0.01)。LPS与IFN-α联用48h后,caspase-8mRNA的表达水平较IFN-α组、LPS组和对照组均升高(P<0.01)。结论:LPS与IFN-α联用能有效抑制白血病细胞的增殖并诱导其凋亡,其机制可能与caspase-8的激活有关。

Objective： To study the synergy effects of lipopolysacchafide （LPS） and interferon-alpha （IFN-α） on the apoptosis of U937 cells, and its clinical mechanism thereof. Methods： U937 cells were treated with 200 μg/L LPS and （or） 2 000 U/mL IFN-α. The inhibitory rate of cells was measured by MTF assay. The apoptotic rate of cells was detected by flow cytometry （FCM）. And the expression of caspase-8 mRNA after 48 h treatment was measured by reverse transcription-polymerase chain reaction （RT-PCR）. Results：There were more pronounced inhibitory effects on U937 cell proliferation and in- creased apoptotic rate after using LPS and IFN-α compared with those of using LPS or IFN-α alone （P 〈 0.01）, and there were significant differences between each drug groups and control group （P 〈 0.01）. The expression level of caspase-8 mRNA increased significantly after 48 h treatment with LPS and IFN-α than that of LPS or IFN-α treatment alone and control group （P 〈 0.01）. Conclusion： LPS in combination with IFN-α can inhibit the proliferation and induce the apoptosis of U937 leukemia cells, which may be related with the activation of caspase-8.