硼替佐米联合低浓度阿糖胞苷诱导U937细胞凋亡的研究

Effect of Bortezomib and Low Concentration Cytarabine on Apoptosis in U937 Cell Line

本研究探讨蛋白酶体抑制剂硼替佐米联合低浓度阿糖胞苷(Ara-C)对U937细胞株的作用及机制。通过细胞计数,细胞形态学检查,流式细胞术和Western blot方法检测硼替佐米(10 nmol/L)和(或)Ara-C(50 nmol/L)处理前后U937细胞的增殖抑制和凋亡及其机制。结果显示,硼替佐米和Ara-C单药均能抑制U937细胞增殖,两药联合的抑制作用更加明显,细胞增殖抑制率在24和48 h分别达(55.00±2.81)%和(70.02±3.33)%;硼替佐米联合低浓度Ara-C能协同诱导U937细胞凋亡,促使线粒体跨膜电位下降,阳性细胞率达(38.70±1.54)%。两药联合应用还能协同诱导caspase-9,-8,-3的活化。结论:硼替佐米联合低浓度Ara-C主要通过线粒体途径、可能还通过死亡受体途径诱导U937细胞凋亡。

This study was aimed to explore the effect of bortezomib and low concentration cytarabine（Ara-C） on proliferation and apoptosis in U937 cell line and its mechanism.The proliferation and apoptosis of U937 cells treated with bortezomib（10 nmol/L） and（or） Ara-C（50 nmol/L） were observed by cell count,cell morphology,flow cytometry and Western blot.The results showed that bortezomib and Ara-C alone inhibited U937 cell proliferation.The inhibitory effect was enhanced by combination of these two drugs,the inhibitory rates of U937 cell proliferation were（55.00±2.81）% and（70.02±3.33）% after treatment for 24 h and 48 h,repectively.Bortezomib and Ara-C synergistically induced apoptosis and decreased mitochondrial membrane potential in U937 cells.The percentage of Rhodamin123 positive cells was（38.70±1.54）%.Bortezomib and Ara-C also synergistically induced activation of caspase-9,caspase-8 and caspase-3.It is concluded that the bortezomib and low concentration Ara-C synergistically induced apoptosis in U937 cells,mainly through mitochondrial pathway,and possibly through death receptor pathway.