【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-Fe₃O₄）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-Fe₃O₄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-Fe₃O₄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-Fe₃O₄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-Fe₃O₄组的细胞凋亡率显著增加,结果提示MNPs-Fe₃O₄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-Fe₃O₄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-Fe₃O₄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。更多还原

【Abstract】 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 copolymer 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.更多还原