This study aimed to characterize the relationship between the COX2 and ALOX5 genes, as well as their link with the multidrug resistance (MDR) phenotype in sensitive (K562) and MDR (K562-Lucena and FEPS) erythroleukemia cells. For this, the inhibitors of 5-LOX (zileuton) and COX-2 (acetylsalicylic acid-ASA) and cells with the silenced ABCB1 gene were used. The treatment with ASA caused an increase in the gene expression of COX2 and ABCB1 in both MDR cell lines, and a decrease in the expression of ALOX5 in the FEPS cells. Silencing the ABCB1 gene induced a decrease in COX2 expression and an increase in the ALOX5 gene. Treatment with zileuton did not alter the expression of COX2 and ABCB1. Cytometry data showed that there was an increase in ABCB1 protein expression after exposure to ASA. In addition, the increased activity of ABCB1 in the K562-Lucena cell line indicates that ASA may be a substrate for this efflux pump, corroborating the molecular docking that showed that ASA can bind to ABCB1. Regardless of the genetic alteration in COX2 and ABCB1, the direct relationship between these genes and the inverse relationship with ALOX5 remained in the MDR cell lines. We assume that ABCB1 can play a regulatory role in COX2 and ALOX5 during the transformation of the parental cell line K562, explaining the increased gene expression of COX2 and decreased ALOX5 in the MDR cell lines.

本研究旨在表征COX2和ALOX5基因之间的关系，以及它们与敏感 (K562) 和 MDR（K562-Lucena 和 FEPS）红白血病细胞中多药耐药 (MDR) 表型的联系。为此，使用了 5-LOX（齐留通）和 COX-2（乙酰水杨酸-ASA）抑制剂以及具有沉默ABCB1基因的细胞。 ASA 处理导致两种 MDR 细胞系中COX2和ABCB1基因表达增加，以及 FEPS 细胞中ALOX5表达减少。沉默ABCB1基因会导致COX2表达减少和ALOX5基因表达增加。齐留通治疗不会改变COX2和ABCB1 的表达。细胞计数数据显示，暴露于 ASA 后 ABCB1 蛋白表达有所增加。此外，K562-Lucena 细胞系中 ABCB1 活性的增加表明 ASA 可能是该外排泵的底物，证实了分子对接表明 ASA 可以与 ABCB1 结合。无论COX2和ABCB1的遗传改变如何，这些基因之间的直接关系以及与ALOX5的负相关关系在 MDR 细胞系中仍然存在。我们假设ABCB1在亲本细胞系K562的转化过程中可以对COX2和ALOX5发挥调节作用，这解释了MDR细胞系中COX2基因表达的增加和ALOX5基因表达的减少。