Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, People's Republic of China.
Int J Nanomedicine. 2010 Nov 19;5:999-1004. doi: 10.2147/IJN.S14957.
The purpose of this study was to investigate the potential effects of combination therapy using magnetic nanoparticles of Fe₃O₄ (MNP-Fe₃O₄) and chemotherapeutic drugs on lymphoma cells. Proliferation, inhibition, and viability of Raji cells were detected by MTT and trypan blue exclusion. The percentage of cells undergoing apoptosis was detected by flow cytometry using fluorescein isothiocyanate-annexin V and propidium iodide staining. p53 and nuclear factor-κB (NF-κB) protein levels were measured by Western blot. The results showed that proliferation of Raji cells was inhibited by adriamycin or daunorubicin in a dose-and time-dependent manner. Cell sensitivity was improved and the 50% inhibitory concentrations of adriamycin and daunorubicin decreased when combined with a MNP-Fe₃O₄ carrier. Interestingly, increased apoptosis in Raji lymphoma cells was accompanied by upregulation of p53 protein and downregulation of NF-κB protein. Furthermore, the combination of MNP-Fe₃O₄ with adriamycin or daunorubicin increased p53 protein levels and decreased NF-κB protein levels more than adriamycin or daunorubicin alone, indicating that MNP-Fe₃O₄ could enhance the effect of chemotherapeutic drugs on p53 and NF-κB. Similar results for cell apoptosis and protein expression were not observed for the groups treated with dexamethasone ± MNP-Fe₃O₄ (P > 0.05). These findings suggest a potential clinical application for MNP-Fe₃O₄ in combination with daunorubicin or adriamycin in the treatment of lymphoma.
本研究旨在探讨磁性四氧化三铁纳米粒子（MNP-Fe₃O₄）与化疗药物联合治疗对淋巴瘤细胞的潜在影响。通过 MTT 和台盼蓝排斥试验检测 Raji 细胞的增殖、抑制和活力。通过荧光素异硫氰酸酯-膜联蛋白 V 和碘化丙啶染色的流式细胞术检测细胞凋亡的百分比。通过 Western blot 测定 p53 和核因子-κB（NF-κB）蛋白水平。结果表明，阿霉素或柔红霉素呈剂量和时间依赖性抑制 Raji 细胞的增殖。与 MNP-Fe₃O₄ 载体结合时，细胞敏感性提高，阿霉素和柔红霉素的 50%抑制浓度降低。有趣的是，Raji 淋巴瘤细胞凋亡增加伴随着 p53 蛋白上调和 NF-κB 蛋白下调。此外，与阿霉素或柔红霉素单独使用相比，MNP-Fe₃O₄ 与阿霉素或柔红霉素联合使用可增加 p53 蛋白水平并降低 NF-κB 蛋白水平，表明 MNP-Fe₃O₄ 可增强化疗药物对 p53 和 NF-κB 的作用。用地塞米松±MNP-Fe₃O₄ 处理的各组在细胞凋亡和蛋白表达方面未观察到类似的结果（P>0.05）。这些发现表明，MNP-Fe₃O₄ 与柔红霉素或阿霉素联合治疗淋巴瘤具有潜在的临床应用前景。
