^(131)I-GM-CSF诱导HL-60细胞凋亡机制的体外研究

^(131)I-GM-CSF induced apoptosis of HL-60

目的:观察131I-GM-CSF诱导HL-60细胞凋亡及其机制,探讨其在急性髓系白血病放射导向治疗中的作用。方法:采用MTT法、TUNEL、透射电子显微镜研究131I-GM-CSF辐射后HL-60细胞的存活率、凋亡率和形态的改变;用流式细胞术和免疫细胞化学方法检测线粒膜电位的改变以及凋亡相关基因的表达。结果:放射性浓度≥18.5×108Bq/L时HL-60细胞存活率显著下降。131I-GM-CSF能致HL-60细胞凋亡、超微结构破坏、线粒体膜电位降低。在诱导细胞凋亡过程中,p53表达上调,bcl-2、bcl-xl表达下调。结论:GM-CSF作为载体携带131I能诱导HL-60细胞凋亡,具有抗白血病的作用。其诱导凋亡的机制与上调p53,下调bcl-2、bcl-xl,开放线粒体膜的通透性转换孔,降低线粒体膜电位有关。

Objective:To investigate the effect and mechanism of apoptosis of HL-60 cells induced by 131 I-GM-CSF.Methods:The relevant data were collected from tetrazolium microculture(MTT)cellular cytotoxicity test,TUNEL technology,transmission electron microscopy,flow cytometric analysis and immunocytochemistry assay.Results:When the radioative dose was higher than 18.5×108Bq/L,cell survival rate was markedly decreased.Cell apoptosis rate was significantly increased and cellular ultrastructure was markedly destroyed by 131 I-GM-CSF.Loss of mitochondrial transmembrane potential(MTP) was found in cells treated with 131 I-GM-CSF.The p53 expression was up regulated ,while those of bcl-2 and bcl-xl were decreaded.Conclusion:These results show that 131 I-GM-CSF can induce significant apoptosis of HL-60 by opening the mitochondrial permeability transition pore and reducing MTP,which suggests that 131 I-GM-CSF may be available in treatment of AML.