载多柔比星磁性纳米颗粒逆转人骨肉瘤细胞多药耐药性的实验研究  

Experimental research on reversal of multidrug resistance in human osteosarcoma cells by doxorubicin loaded magnetic nanoparticles

作　　者：郑铁钢[1] 郭全义[2] 陈继营[2] 贾艳辉[1] 张罕[2] 崔雪梅[2] 袁玫[2] 卢世璧[2] 

机构地区：[1]解放军第二五一医院骨科,张家口075000 [2]解放军总医院骨科研究所

出　　处：《肿瘤研究与临床》2015年第6期361-364,370,共5页Cancer Research and Clinic

基　　金：国家863计划项目（2007AA021806）

摘　　要：目的 探讨载多柔比星磁性纳米颗粒（DOX-MNP）逆转人骨肉瘤细胞多药耐药性的可行性.方法 以人骨肉瘤多药耐药细胞株R-OS-732为实验对象,应用荧光显微镜观察DOX-MNP进入肿瘤细胞及其在细胞内分布的情况,采用四甲基偶氮唑蓝比色（MTT）法检测DOX-MNP对肿瘤细胞的增殖活性的影响,采用Annexin V-FITC/PI染色,流式细胞术检测DOX-MNP对肿瘤细胞凋亡的影响.结果 荧光显微镜观察发现与游离DOX相比,DOX-MNP在肿瘤细胞内尤其在细胞核内积聚更多;MTT实验表明DOX-MNP抑制肿瘤细胞增殖的效应较游离DOX更强;流式细胞术结果表明DOX-MNP促进肿瘤细胞坏死,而游离DOX促进细胞凋亡.结论 DOX-MNP对人骨肉瘤多药耐药细胞株R-OS-732的体外杀伤效应较游离DOX更强,能够逆转其多药耐药性.Objective To investigate the effect of doxorubicin loaded magnetic nanoparticles （DOX-MNP） on reversal of multidrug resistance in human osteosarcoma cell line R-OS-732 in vitro.Methods The cellular uptake and intracellular distribution of DOX-MNP were visualized by virtue of the intrinsic red fluorescence of doxorubicin under a fluorescence microscopy.The inhibitory effect of DOX-MNP on proliferation of R-OS-732 cells was assayed by MTT method.The influence on apoptosis of DOX-MNP was analysed using Annexin V-FITC/PI staining by flow cytometry.Results Compared with free doxorubicin,DOX-MNP showed more iutracellular uptake,increased accumulation in the nucleus and enhanced antiproliferative effect against R-OS-732 cells.DOX-MNP showed increased necrosis rather than apoptosis in R-OS-732 cells.Conclusion DOX-MNP has pronounced antiproliferative effect against multidrug resistant human osteosarcoma cells in vitro,providing a new strategy for reversal of multidrug resistance.

关 键 词：骨肉瘤 多柔比星 纳米颗粒 细胞毒性 

分 类 号：R738[医药卫生—肿瘤]