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本研究旨在探讨铁螯合剂去铁胺对人白血病耐阿霉素细胞K562/A02的影响及其作用机制。采用四甲基偶氮唑蓝法(MTT)检测不同浓度去铁胺作用48小时对K562/A02细胞增殖的抑制效应;流式细胞术检测去铁胺25、50、100和200μmol/L作用K562/A02细胞48小时后细胞的凋亡率;半定量RT-PCR检测各组细胞凋亡基因BAX、BCL-2以及多药耐药基因1(MDR1)mRNA表达变化;Western blot检测各组细胞P-糖蛋白(P-gp)表达变化。结果显示,随着去铁胺药物浓度的增加,细胞活力逐渐下降,凋亡率明显增加,呈剂量依赖性;随着去铁胺浓度增加,BAX表达水平逐渐升高,但MDR1 mRNA与P-gp的表达受到显著抑制。结论:去铁胺可以通过螯合细胞内铁,影响细胞DNA的合成;同时去铁胺可抑制阿霉素诱导的MDR1、P-gp表达,增加白血病细胞对化疗药物的敏感性,进而诱导凋亡。
This study aimed to investigate the effect of iron chelator deferoxamine on doxorubicin-resistant cells K562 / A02 in human leukemia and its mechanism. The inhibitory effect of different concentrations of deferoxamine on the proliferation of K562 / A02 cells was detected by MTT assay. The effects of deferoxamine at 25, 50, 100 and 200 μmol / L K562 were detected by flow cytometry / A02 cells 48h after the apoptosis rate; semi-quantitative RT-PCR detection of apoptotic gene BAX, BCL-2 and multidrug resistance gene 1 (MDR1) mRNA expression changes; Western blot detection of each group of cells P - Glycoprotein (P-gp) expression changes. The results showed that with the increase of deferoxamine concentration, cell viability decreased and apoptosis rate increased significantly in a dose-dependent manner. With the increase of deferoxamine concentration, the expression of BAX increased gradually, but the expression of MDR1 mRNA and P- gp expression was significantly inhibited. Conclusion: Desferrioxamine can affect the DNA synthesis by chelating intracellular iron. At the same time, desferrioxamine can inhibit doxorubicin-induced MDR1 and P-gp expression and increase the sensitivity of leukemia cells to chemotherapeutics, Death.