在此研究中，我们发现不同化疗药物可能选择具有不同抗氧化能力的细胞。为此，我们评估了两种多药耐药（MDR）红白血病细胞系Lucena（对长春新碱（VCR）耐药）和FEPS（对多柔比星（DNR）耐药）对过氧化氢的敏感性。它们来源于同一敏感细胞K562（非MDR）。此外，我们还评估了这些细胞系在没有VCR/DNR的氧化剂存在下的反应。在没有VCR的情况下，当暴露于过氧化氢时Lucena的细胞存活率急剧下降，而FEPS即使没有DNR也不会受影响。为了分析不同化疗药物的选择是否会产生不同的能量需求，我们分析了反应性氧化物种（ROS）的产生和葡萄糖转运蛋白1基因（GLUT1）的相对表达。我们观察到，经过DNR的选择显然比VCR产生更高的能量需求。即使DNR从FEPS培养基中撤出一个月，也仍保持了转录因子基因（NRF2，HIF-1α和OCT4）高水平的表达。这些结果表明，DNR选择具有更大能力表达与抗氧化防御系统相关的主要转录因子以及与MDR表型相关的主要外排泵（ABCB1）的细胞。考虑到肿瘤细胞的抗氧化能力与对多种药物的抵抗力密切相关，因此显然内源性抗氧化分子可能是开发新的抗癌药物的目标。 ©2023年。作者（们）独家授权Springer Science+Business Media，LLC，Springer Nature的一部分。

In this work, we identified that different chemotherapeutic drugs may select cells with different antioxidant capacities. For this, we evaluated the sensitivity of two multidrug-resistant (MDR) erythroleukemia cell lines: Lucena (resistant to vincristine, VCR) and FEPS (resistant to daunorubicin, DNR) derived from the same sensitive cell K562 (non-MDR) to hydrogen peroxide. In addition, we evaluated how the cell lines respond to the oxidizing agent in the absence of VCR/DNR. In absence of VCR, Lucena drastically decreases cell viability when exposed to hydrogen peroxide, while FEPS is not affected even without DNR. To analyze whether selection by different chemotherapeutic agents may generate altered energetic demands, we analyzed the production of reactive oxygen species (ROS) and the relative expression of the glucose transporter 1 gene (glut1). We observed that the selection through DNR apparently generates a higher energy demand than VCR. High levels of transcription factors genes expression (nrf2, hif-1α, and oct4) were kept even when the DNR is withdrawn from the FEPS culture for one month. Together, these results indicate that DNR selects cells with greater ability to express the major transcription factors related to the antioxidant defense system and the main extrusion pump (ABCB1) related to the MDR phenotype. Taking into account that the antioxidant capacity of tumor cells is closely related to resistance to multiple drugs, it is evident that endogenous antioxidant molecules may be targets for the development of new anticancer drugs.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.