纳米雄黄对白血病K562细胞及其干细胞的凋亡诱导作用  

The apoptosis effects of leukemia stem cells induced by nano-realgar in leukemia cells

作　　者：周思彤[1] 王永胜[2] 易娟 陈静[3] 魏虎来[3] 

机构地区：[1]甘肃省中医院检验科 [2]甘肃省中医药研究院 [3]兰州大学基础医学院甘肃省新药临床前研究重点实验室,兰州730000

出　　处：《中药药理与临床》2013年第2期105-108,共4页Pharmacology and Clinics of Chinese Materia Medica

基　　金：甘肃省中医药科学技术研究课题(GZK-2010-17);甘肃省自然科学研究基金计划项目(096RJZA034);甘肃省新药临床前研究重点实验室(兰州大学)开放课题(GSKFKT-0802)资助

摘　　要：目的:研究纳米雄黄对白血病K562细胞及其白血病干细胞的凋亡诱导作用。方法:采用机械研磨法制备纳米雄黄。以白血病K562细胞为靶细胞,MTT法检测K562细胞增殖活性,采用流式细胞术检测K562细胞凋亡率、P-gp和BCRP蛋白的表达水平,以及白血病干细胞含量变化及其凋亡。结果:雄黄经高能球磨机球磨10～50h,扫描电镜(SEM)和透射电镜(TEM)观察,电镜测量纳米雄黄的平均粒径为72.72±22.18 nm。20μg/ml和50μg/ml纳米雄黄及雄黄原药处理K562细胞后,纳米雄黄对K562细胞有明显的增殖抑制作用,24h、48h、72h的IC50值分别为43.48μg/ml、20.52μg/ml、16.07μg/ml。细胞的凋亡率明显升高。雄黄原药对K562细胞也有增殖抑制及凋亡诱导作用,但效果要差于纳米雄黄。BCRP、P-gp蛋白表达以及二者共表达率随着时间的延长和浓度的增高呈上升趋势,尤以高浓度时明显。20μg/ml和50μg/ml纳米雄黄处理K562细胞24h,LSC含量随浓度升高而升高,K562细胞群中LSC的凋亡率升高。结论:纳米雄黄可诱导药物敏感性白血病细胞及其白血病干细胞发生凋亡。To explore apoptosis-inducing effects of realgar nanopartide （nano-realgar） on leukemia stem cells. Methods： Preparation of nano-realgar was mechanical milled using a high-energy planetary ball mill. Using leukemia cells （K562） as target ceils, Flow cytometry （FCM） was employed to assess the expression of intraceilular P-glycoprotein（ P-gp）, breast cancer resistance protein（ BCRP）, the changing of leukemia stem cells contents and the apoptosis of leukemia stem ceils. Results： Treated cells for 24h and 48h with 20p.g/ml and 50p.g/ml nano-realgar, the apoptosis of K562 ceils detected by Annexin V/PI staining was increased. BCRP and P-gp expression increased, Co-ex- pression of BCRP and P-gp protein were increased. The three concentrations （0μg/ml, 20μg/ml, 50μg/ml） in nano-realgar treated cells 24h, the relative content of LSCs in K562 increased, apoptosis rate increased in LSCS in the group of K562 cells. Conclusion： Nano-Realgar significantly induced apoptesis of leukemia stem cells in leukemia cells.

关 键 词：纳米雄黄 白血病干细胞 细胞凋亡 

分 类 号：R285[医药卫生—中药学]