去铁胺和三氧化二砷对 APL 样细胞系活力和活力的联合作用。
Combination Effect of Deferoxamine and Arsenic Trioxide on Viability and Vitality of APL Like Cell Line.
发表日期:2023 Jul
作者:
Kazem Ghaffari, Ali Bayat, Ali Ghasemi
来源:
Experimental Hematology & Oncology
摘要:
三氧化二砷是治疗急性早幼粒细胞白血病(APL)的活性剂,单独作用,但对患者有不良影响。此外,去铁胺具有抗增殖活性并诱导白细胞减少症。为了增强三氧化二砷的抗白血病效果并减少三氧化二砷的用量,本实验研究了三氧化二砷与去铁胺(DFO)联合使用对APL细胞系(NB4)的细胞毒作用。在急性早幼粒细胞白血病中,用不同剂量处理NB4细胞系(伊朗巴斯德研究所提供),然后分别以24小时、48小时和72小时为间隔,研究存活百分比、细胞计数、代谢活性和凋亡诱导。 。此外,通过RT-PCR方法分析了hTERT基因表达。我们发现DFO单独以及与ATO组合具有细胞毒性和抗增殖作用,并以剂量和时间依赖性方式降低NB4细胞系的活力和细胞代谢活性。此外,这种组合会导致细胞中细胞凋亡增加、Caspase-3 上调和 hTERT 基因下调。ATO/DFO 联合治疗协同降低了 hTERT 的 mRNA 水平,并增加了 Caspase-3 的 mRNA 水平。 3 与单独使用 DFO 相比,以时间依赖性方式实现。© 2023 Kazem G., et al.
Arsenic trioxide is an activist agent in the treatment of acute promyelocytic leukemia (APL), which acts alone, but has an adverse effect on patients. Moreover, deferoxamine has antiproliferative activity and induces leukopenia. In order to enhance antileukemic effectiveness and to reduce the dosage of arsenic trioxide, the combination effect of it with deferoxamine (DFO) was evaluated on the APL cell line (NB4).In this experimental study, to investigate the cytotoxic effects of ATO/DFO in acute promyelocytic leukemia, the NB4 cell line (provided by Pasteur Institute of Iran) was treated with different doses and then at 24, 48, and 72 hrs intervals, the percentage of survival, cell count, metabolic activity and apoptosis induction were investigated respectively. Also, hTERT gene expression was analyzed by the RT-PCR method.We found that DFO alone and in combination with ATO has cytotoxic and antiproliferative effects, and reduces viability and cell metabolic activity in the NB4 cell line in a dose and time-dependent manner. In addition, this combination causes an increase in apoptosis, up-regulation of Caspase-3, and down-regulation of hTERT genes in cells.Combined ATO/ DFO treatment cooperatively decreased the mRNA levels of the hTERT and increased the mRNA levels of Caspase-3 in a time-dependent manner compared to DFO alone.© 2023 Kazem G., et al.