Fe_3O_4磁性纳米粒子增强青蒿琥酯诱导SKM-1细胞凋亡(英文)

Magnetic Nanoparticles of Fe_3O_4 Enhance Artesunate-inducing Apoptosis of SKM-1 Cells

目的:研究磁性纳米粒子Fe_3O_4和青蒿琥酯共聚物对MDS细胞株SKM-1细胞的抑制作用和潜在的机制。方法:用蛋白质印记法检测用或不用共聚物治疗SKM-1细胞的BCL-2、BAX、Caspase-3和Survivin的蛋白表达水平。用流式细胞术检测共聚物诱导的SKM-1细胞的凋亡率。结果:共聚物组的细胞凋亡率明显高于磁性纳米粒子Fe_3O_4组和青蒿琥酯组,磁性纳米粒子Fe_3O_4可以增强青蒿琥酯诱导SKM-1细胞凋亡。蛋白质印记法结果显示,Survivin和BCL-2在青蒿琥酯组表达下调,并且这个下调在青蒿琥酯和磁性纳米粒子Fe_3O_4共聚物组更为明显。与对照组和磁性纳米粒子Fe_3O_4组相比,青蒿琥酯组和共聚物组的BAX水平增高。当青蒿琥酯结合磁性纳米粒子Fe_3O_4后活性Caspase-3水平明显上调。青蒿琥酯和磁性纳米粒子Fe_3O_4共聚物会激发SKM-1细胞凋亡相关基因表达水平的改变,其中BAX的上调与Survivin和BCL-2的下调是主要改变。结论:青蒿琥酯可以诱导SKM-1细胞的凋亡,磁性纳米粒子Fe_3O_4可增强青蒿琥酯诱导细胞凋亡的作用。

Objective:To investigate the inhibitory effect of the copolymer of magnetic nanoparticles of Fe_3O_4(MNPs-Fe_3O_4) and artesunate(ART) on myelodysplastic syndromes(MDS) cell line SKM-1 cells and the potential mechanisms.Methods:The protein expression levels of BCL-2.,BAX,Caspase-3,and Survivin in SKM 1 cells treated with or without the co-polymer were measured by Western blot.The co-polymer-induced apoptosis rate of SKM-1 cells was measured by flow cytometry.Results:The apoptosis rate of SKM-1 cells in the copolymer groups was higher than that in both MNPs-Fe_3O_4 and artesunate groups alone.The MNPs-Fe_3O_4 may enhance ART induced cell apoptosis.Western blot assay showed that the expression of survivin and BCL-2 protein were down-regulated in the ART group,and this down-regulation was even more significant in the group of copolymer of ART with MNPs-Fe_3O_4.The levels of BAX were increased both in ART group and the copolymer of ART with MNPs-Fe_3O_4 group,as compared with control group and MNPs-Fe_3O_4 group.The levels of active-caspase-3 were obviously up-regulated when the ART was combined with the MNPs-Fe_3O_4.The copolymer of ART with MNPs-Fe_3O_4 could trigger changes in the expression levels of apoptosis-related genes in SKM-1 cells,among which up-regulation of BAX and down-regulation of survivin and BCL-2 are the 2 major alterations.Conclusion:Artesunate can induce the apoptosis of SKM-1 cells,and MNPs-Fe_3O_4 may enhance the cell apoptosis induced by ART.