张静宜,范 丹,肖 方,李媛春,熊春雷.三氧化二砷通过激活Drp-1增加人白血病HL-60细胞的放疗敏感性[J].,2017,17(17):3206-3210 |
三氧化二砷通过激活Drp-1增加人白血病HL-60细胞的放疗敏感性 |
Arsenic Trioxide Renders Human Leukemia HL-60 Cells More Sensitive to Radiation via Activating Drp-1 |
投稿时间:2016-12-09 修订日期:2016-12-29 |
DOI:10.13241/j.cnki.pmb.2017.17.002 |
中文关键词: 三氧化二砷 Drp-1 凋亡 线粒体 HL-60细胞 |
英文关键词: Arsenic trioxide Drp-1 Apoptosis Mitochondria HL-60 cells |
基金项目:国家自然科学基金项目(31572344) |
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中文摘要: |
摘要 目的:研究三氧化二砷(Arsenic trioxide,ATO)对人白血病HL-60细胞放疗敏感性的影响,并以动力相关蛋白-1(dynamin-re- lated protein 1, Drp-1)为靶点探讨其可能的机制。方法:1 μg/mL浓度的ATO处理HL-60细胞后使用20Gy强度进行放疗,采用MTT法检测细胞活力,流式细胞术检测细胞凋亡,通过线粒体钙离子缓冲能力检测线粒体钙离子代谢障碍,采用免疫印迹法检测Drp-1蛋白表达,并通过Drp-1阻滞剂mdivi-1预处理的方法检测Drp-1在实验中的作用。结果:1 μg/mL浓度的 ATO对HL-60细胞活力无影响,但可显著增加20Gy放疗所致的细胞活力下降、细胞凋亡和线粒体钙离子代谢障碍;1 μg/mL浓度的 ATO可显著增加Drp-1蛋白表达,使用mdivi-1预处理可部分逆转ATO的放疗增敏作用。结论:一定剂量的ATO可增加人白血病HL-60细胞的放疗敏感性,而这一作用可能是通过激活Drp-1蛋白表达而实现。 |
英文摘要: |
ABSTRACT Objective: To investigate the effect of arsenic trioxide (ATO) on radiation sensitivity in human leukemia HL-60 cells, and also elucidate the potential mechanism with focus on dynamin-related protein 1 (Drp-1). Methods: After treatment with 1 μg/mL ATO, HL-60 cells were exposed to radiation at 20 Gy. The cell viability was assayed by MTT method, apoptotic cell death was detected by flow cytometry and mitochondrial calcium metabolism dysfunction was determined by measuring mitochondrial calcium buffering ca- pacity. The expression of Drp-1 protein was detected by western blot, and the involvement of Drp-1 was investigated by pretreatment with the Drp-1 inhibitor mdivi-1. Results: ATO at the concentrations of 1 μg/mL had no effect on cell viability in HL-60 cells, whereas promoted the 20 Gy radiation-induced cell viability loss, apoptotic cell death and mitochondrial calcium metabolism dysfunction. ATO at the concentrations of 1 μg/mL increased the expression of Drp-1 protein, and pretreatment with mdivi-1 partially prevented the in- creased radiation sensitivity induced by ATO. Conclusion: Arsenic trioxide renders human leukemia HL-60 Cells more sensitive to radi- ation through activating Drp-1. |
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