磁性纳米四氧化三铁增强青蒿琥酯诱导的K562细胞凋亡及作用机制研究  

Enhancement of the Artesunate-induced Apoptosis of K562 Cells by Magnetic Nanoparticles of Fe_3O_4 and Their Related Mechanism

作　　者：韩玉祥[1] 王颖[2] 杨营营[2] 杨敬慈[2] 郭晓楠[2] 张静楠[2] 姚丽[2] 尚银涛[2] 王兴哲[2] 王茜[2] 潘崚[2] 

机构地区：[1]河北医科大学第二医院免疫风湿科,石家庄市050000 [2]河北医科大学第二医院血液内科,石家庄市050000

出　　处：《中国肿瘤临床》2011年第21期1310-1314,共5页Chinese Journal of Clinical Oncology

摘　　要：目的:本研究旨在观察青蒿琥酯共聚磁性纳米四氧化三铁(MNPs-Fe_3O_4)后,对K562细胞的细胞毒性效应以及是否增加K562细胞的凋亡,了解MNPs-Fe_3O_4是否可以增强青蒿琥酯的活性,并进一步探讨其可能的机制。方法:采用Western印迹检测K562细胞Bcl-2、Bax、Bcl-rambo,激活的Caspase-3和Survivin蛋白的表达,应用MTT法检测青蒿琥酯共聚MNPs-Fe_3O_4后对K562的细胞毒性,用流式细胞仪检测K562细胞的凋亡率。结果:青蒿琥酯可以抑制K562细胞的增殖,当青蒿琥酯共聚MNPs-Fe_3O_4后,对K562细胞的增殖抑制率显著高于单用青蒿琥酯组(P<0.05),同时检测细胞凋亡率也发现,与单用青蒿琥酯组相比,青蒿琥酯共聚MNPs-Fe_3O_4组的细胞凋亡率显著增加,结果提示MNPs-Fe_3O_4可以增强青蒿琥酯的活性。而当加入泛Cas-pase抑制剂Z-VAD-FMK以后,MNPs-Fe_3O_4增强青蒿琥酯诱导细胞死亡的效应则被减弱了。Western印迹显示,青蒿琥酯共聚MNPs-Fe_3O_4组与单用青蒿琥酯组相比,Bcl-2,Bax,Bcl-rambo和Caspase-3蛋白的表达上调,而Survivin蛋白的表达则是下调的。结论:磁性纳米四氧化三铁可以增强青蒿琥酯诱导的K562细胞凋亡,其机制可能与上调Bcl-rambo和下调Survivin蛋白有关。Objective： To investigate the growth inhibition effect of a copolymer composed of artesunate （ ART ） and magnetic nanoparticles of Fe3O4 （ MNPs-Fe3O4 ） on K562 cells and explore its potential mechanisms. Methods： The protein expression levels of Bcl-2, Bax, Bcl-rambo, Caspase-3, and Survivin in K562 cells treated with or without the copolymer of ART with MNPs-Fe3O4 were measured by Western blot. The cytotoxicity of the copolymer on K562 cells was determined by an MTT assay. The copolymer-induced apoptosis rate of K562 cells was measured by flow cytometry. Results： ART could inhibit the proliferation of K562 cells. When treated with the copolymer of ART with MNPs-Fe3O4, the K562 cell proliferation inhibition rate was significantly increased compared with that of K562 cells treated with ART alone （ P 〈 0.05 ）. Flow cytometry results demonstrated that the apoptosis rate induced by the copolymet more significantly increased than that by ART alone （ P 〈 0.05 ）. These results suggest that MNPs-Fe3O4 can enhance the activity of ART. Interestingly, copolymer-induced cell death was attenuated by the caspase inhibitor Z-VAD-FMK. The results also indicate that when compared with ART alone, the copolymer of MNPs-Fe3O4 and ART up-regulates the expression of Bcl-2, Bax, Bcl-rambo, and Caspase-3 proteins in K562 cells, but down-regulates the expression of Survivin protein. Conclusion： The results suggest that MNPs-Fe3O4 synergistically increases the apoptosis induced by ART in K562 cells, which may be related to the up-regulation of Bcl-rambo and down-regulation of Survivin.

关 键 词：青蒿琥酯 磁性纳米四氧化三铁 K562细胞 凋亡 

分 类 号：R965[医药卫生—药理学]