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四氧化三铁磁性纳米粒子和 5-溴脱氧吴茱萸碱对 K562/A02 白血病细胞多药耐药的逆转作用。

Effect of magnetic nanoparticles of Fe3O4 and 5-bromotetrandrine on reversal of multidrug resistance in K562/A02 leukemic cells.

机构信息

Department of Hematology, The Affiliated Zhongda Hospital, Southeast University, Nanjing 210009, People's Republic of China.

出版信息

Int J Nanomedicine. 2009;4:209-16. doi: 10.2147/ijn.s7090. Epub 2009 Oct 19.

Abstract

This study aims to evaluate the multidrug resistance (MDR) reversal activity by magnetic nanoparticles of Fe3O4 (MNPs-Fe3O4) and 5-bromotetrandrine (BrTet) MDR cell line K562/A02 solitarily or symphysially. The proliferation of K562 and K562/A02 cells and the cytotoxicity on peripheral blood mononuclear cells (PMBCs) were evaluated by MTT assay. Cellular accumulation of daunorubicin (DNR) was analyzed by flow cytometry. Real-time polymerase chain reaction and Western blotting analyses were performed to examine the mRNA and protein levels of mdr1, respectively. The results showed that the combination of MNPs-Fe3O4 and BrTet with effective concentrations significantly increased cytotoxicity against MDR cell line K562/A02. Both BrTet and MNPs-Fe3O4 increased the intracellular DNR accumulation in the K562/A02 cell line, and downregulated the level of mdr1 gene and expression of P-glycoprotein. Furthermore, the combination did not have significant cytotoxicity in PMBCs. We propose that MNPs-Fe3O4 conjugated with DNR and BrTet probably have synergetic effects on MDR reversal.

摘要

本研究旨在评估磁性纳米粒子 Fe3O4(MNPs-Fe3O4)和 5-溴代汉防己甲素(BrTet)对 K562/A02 耐药细胞系单独或联合应用的多药耐药(MDR)逆转活性。采用 MTT 法检测 K562 和 K562/A02 细胞的增殖及对人外周血单个核细胞(PMBCs)的细胞毒性。采用流式细胞术分析柔红霉素(DNR)的细胞内蓄积。实时聚合酶链反应和 Western blot 分析分别用于检测 mdr1 的 mRNA 和蛋白水平。结果表明,有效浓度的 MNPs-Fe3O4 和 BrTet 联合应用显著增加了对 MDR 细胞系 K562/A02 的细胞毒性。BrTet 和 MNPs-Fe3O4 均增加了 K562/A02 细胞系内 DNR 的蓄积,并下调了 mdr1 基因的水平和 P-糖蛋白的表达。此外,该联合用药对 PMBCs 无明显细胞毒性。我们提出,DNR 和 BrTet 偶联的 MNPs-Fe3O4 可能对 MDR 逆转具有协同作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8229/2775691/8fa9dfdda2f1/ijn-4-209f1.jpg

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