摘要
目的:探讨四氧化三铁磁性纳米颗粒(Fe3O4-MNP)联合三氧化二砷(As2O3)及阿霉素(ADM)对非霍奇金淋巴瘤细胞株Raji凋亡和自噬的影响。方法:MTT法测定单药和联合用药后Raji细胞的生长抑制率;流式细胞术检测凋亡细胞及细胞内ADM浓度;蛋白印迹分析法测定凋亡相关蛋白BCL-2、NFκB、Survivin、BAX、P53、Caspase-3,自噬相关蛋白LC3、Beclin-1、P62/SQSTM1的表达水平。结果:ADM联合As2O3能明显抑制Raji细胞的生长,它的抗肿瘤效应强于单用ADM或As2O3组,但弱于ADM+As2O3+Fe3O4-MNP组(P<0.05);ADM+As2O3+Fe3O4-MNP细胞的凋亡率及ADM药物累积量均高于对照组、ADM组、As2O3组及ADM+As2O3组(P<0.05),并且该组细胞中凋亡相关蛋白BCL-2、NFκB、Survivin表达下调幅度和BAX、P53、Caspase-3表达上调幅度均大于其它组(P<0.05),自噬相关蛋白LC3、Beclin-1表达高于其它组,P62/SQSTM1的表达低于其他组(P<0.05)。结论:Fe3O4-MNP联合As2O3和ADM通过促进凋亡和诱导自噬抑制了Raji细胞的生长,提高了抗肿瘤效应,对于恶性淋巴瘤治疗将是一个有前景的新方法。
Objective : To explore the effect of magnetic iron nanoparticles( Fe3O4- MNP) in combination with arsenic trioxide and adriamycin on apoptosis and autophagy of Raji cells,a non-Hodgkin's lymphoma( NHL) cell line.Methods: The growth inhibition rate of Raji cells was analyzed by MTT assay,the cells apoptosis and intracellular concentration of ADM were determined by flow cytometry( FCM),the expression levels of apoptosis-related proteins such as BCL-2,NFκB,Survivin,BAX,P53,and Caspase-3,and related to autophagy-proteins,such as LC3,Beclin-1,and P62 /SQSTM1 were detected by Western blot. Results: The growth inhibition of Raji cells in the group of ADM +As2O3 were higher than that in the group of ADM or As2O3 alone,however,lower than that in the group of Fe3O4-MNP combined with ADM and As2O3( ADM + As2O3 + MNP)( P < 0. 05). The apoptotic rate and accumulation of intracellular ADM in the group of Fe3O4- MNP combined with ADM and As2O3 were significantly higher than those in control,ADM,As2O3,and ADM plus As2O3 groups( P < 0. 05). The upregulation of BAX,P53 and Caspase-3expression and the down regulation of BCL-2,NFκB,and Survivin expression at protein level were more remarkable in the group of ADM + As2O3 + MNP,compared with the other groups( P < 0. 05). Moreover,the expressions of LC3 and Beclin-1 proteins in the group of ADM + As2O3 + MNP were higher,while the expression of P62 /SQSTM1 was lower than that in other groups( P < 0. 05). Conclusion: The Fe3O4- MNP combined with ADM and As2O3 can increase the antitumor efficacy on Raji cells by promoting apoptosis and inducing autophagy. It would be a promising strategy for malignant lymphoma therapy.
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2015年第5期1318-1324,共7页
Journal of Experimental Hematology
基金
南京医科大学科技发展基金重点项目(2012NJMU151)
淮安市科技支撑指导项目(2012HASZ2012011)
