Realgar nano-particles induce apoptosis and necrosis in leukemia cell lines K562 and HL-60

目的:考察雄黄纳米微粒对于HL-60和K562细胞的增殖抑制作用与诱导凋亡及坏死作用,并初步探寻表现药理活性的化学物种.方法:采用"溶剂接力"法制备雄黄纳米微粒悬浮液,应用MTT法检测雄黄纳米微粒对HL-60和K562细胞的增殖抑制作用,通过Annexin V-PI双染流式细胞术和细胞形态学观察检测细胞凋亡和坏死,并以H3AsO3(As2O3在该溶液中的主要存在形式)作为阳性对照.结果:雄黄纳米微粒的平均粒径为159.0 nm.MIT实验结果显示,该制剂对于这2种细胞系均有明显的增殖抑制作用.双染实验表明,雄黄纳米微粒可诱导这2种细胞凋亡和坏死,此结果得到形态学观察的进一步证实.结论:雄黄纳米微粒对于HL-60和562这2种细胞系均具有诱导凋亡和坏死的双重作用,既含有As-0又含有As-S键的硫代亚砷酸盐可能是表现药理活性的主要化学物种之一.To examine the growth-inhibitory, apoptosis- and necrosis-inducing effects of realgar nano-particles (RNP) in human chronic myelogenous leukemia cell line K562 and acute myeloid leukemia cell line HL-60, and to find out the chemical species with efficacy.A "solvent-relay" strategy was used for the preparation of RNP suspension. Cell viability was determined by MTT assay. Cell apoptosis and necrosis were characterized with Annexin V-PI double staining in association with flow cytometry and with morphological examination with Hoechst 33258 staining. Parallel experiments with arsenous acid (H3AsO3), the dominant form of arsenic trioxide in the solution, were conducted for comparison.The mean diameter of RNP was 159.0 nm. RNP showed growth-inhibitory effect on both cell lines. The double staining test indicated that RNP induced both apoptosis and necrosis, and this was further confirmed by morphological examination.RNP induced both apoptosis and necrosis in leukemia cell lines K562 and HL-60. Thioarsenite species with both As-O and As-S bonds may be the active intermediates in the RNP.国家自然科学基金PubMed中文核心期刊要目总览(PKU)中国科学引文数据库(CSCD)02136-1403