Effect of magnetic nanoparticles of Fe3O4 and wogonin on the reversal of multidrug resistance in K562/A02 cell line.
Effect of magnetic nanoparticles of Fe3O4 and wogonin on the reversal of multidrug resistance in K562/A02 cell line.
复制标题
Fe3O4和汉黄芩素磁性纳米粒子对逆转K562/A02细胞系多药耐药性的影响
DOI：
10.2147/ijn.s32065
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发表时间：
2012
影响因子：
8
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Cheng J;Cheng L;Chen B;Xia G;Gao C;Song H;Bao W;Guo Q;Zhang H;Wang X
背景多药耐药是恶性血液病全身化疗有效性的主要障碍。本研究探讨了汉黄芩素和柔红霉素共聚物在Fe_3O_4磁性纳米粒子上的可逆性效应及其可能的作用机制。方法采用MTT法检测柔红霉素对K562/A02细胞的生长抑制率，流式细胞仪检测柔红霉素对K562/A02细胞凋亡及细胞内柔红霉素浓度的影响。透射电镜下观察K562/A02细胞摄取的纳米颗粒的分布，并通过普鲁士蓝染色证实。逆转录聚合酶链反应检测MDR 1 mRNA转录水平，Western blotting检测P-糖蛋白表达。结果柔红霉素-汉黄芩素磁性纳米粒的可逆效应是柔红霉素+汉黄芩素和柔红霉素磁性纳米粒的8.87倍。透射电子显微镜和普鲁士蓝染色显示，纳米颗粒位于胞质内体囊泡。此外，柔红霉素-汉黄芩素磁性纳米粒组中的细胞凋亡率和细胞内柔红霉素的积聚显著高于柔红霉素、柔红霉素+汉黄芩素和柔红霉素磁性纳米粒组。此外，与其他各组相比，柔红霉素汉黄芩素磁性纳米粒组K562/A02细胞MDR 1 mRNA转录和P-糖蛋白表达明显下调。结论柔红霉素-汉黄芩素磁性纳米粒对K562/A02白血病耐药细胞有明显的抑制作用，有望成为克服白血病多药耐药的新策略。
Background Multidrug resistance is the main obstacle to the efficiency of systemic chemotherapy against hematologic malignancy. This study investigated the reversible effect of the copolymer wogonin and daunorubicin coloaded into Fe3O4 magnetic nanoparticles, and the mechanism potentially involved. Methods The growth inhibition rate of K562/A02 cells was investigated by MTT assay, and apoptosis of cells and the intracellular daunorubicin concentration were detected by flow cytometry. Distribution of nanoparticles taken up by K562/A02 cells was observed under a transmission electron microscope and demonstrated by Prussian blue staining. The transcription level of MDR1 mRNA and expression of P-glycoprotein were determined by reverse transcriptase polymerase chain reaction and Western blotting assay, respectively. Results The reversible effect of daunorubicin-wogonin magnetic nanoparticles was 8.87-fold that of daunorubicin + wogonin and of daunorubicin magnetic nanoparticles. Transmission electron microscopy and Prussian blue staining revealed that the nanoparticles were located in the endosome vesicles of cytoplasm. Also, the apoptosis rate and accumulation of intracellular daunorubicin in the daunorubicin-wogonin magnetic nanoparticle group were significantly higher than that in the daunorubicin, daunorubicin + wogonin, and daunorubicin magnetic nanoparticle groups. Furthermore, transcription of MDR1 mRNA and expression of P-glycoprotein in K562/A02 cells were significantly downregulated in the daunorubicin-wogonin magnetic nanoparticle group compared with the other groups. Conclusion These findings suggest that the remarkable effects of the novel daunorubicin-wogonin magnetic nanoparticle formulation on multidrug resistant K562/A02 leukemia cells would be a promising strategy for overcoming multidrug resistance.