Investigating the effect of treating MOLT-4 cells using 5-Azacitidine on the expression of drug resistance genes

Abstract

ALL is the most common malignancy of children and adolescents, which originates from the bone marrow. Chemotherapy plays an important role in the treatment of hematological malignancies. However, the resistance of some tumors to chemotherapy drugs limits the effect of chemotherapy and causes recurrence of the disease. The multidrug resistant (MDR) phenotype is well known in clinical samples and has been extensively studied, especially in acute leukemias. The best characterized resistance mechanism in adult acute leukemia is a gene-mediated mechanism. MDR1 is performed and has been shown to be associated with poor outcome. It has now become clear that other novel proteins may be associated with the multidrug resistant (MDR) phenotype, such as MRP1, which, like MDR1, reduces intracellular drug accumulation by increasing drug secretion. Although the exact mechanism of MRP1-mediated drug transport is still not fully understood, recent studies suggest that MRP1 acts as a transporter of glutathione S-conjugates. The compound 5-Azacitidine with the brand name Vizada is a chemotherapy and neoplastic drug that is widely used in myelodysplastic syndromes and CMML. This DNA demethylating drug can help increase the expression of repressive genes and regulate cell growth. In this study, the effect of demethylating drug 5-Azacitidine on the expression of drug resistance genes MDR1 and MPR1 in MOLT-4 cell line is investigated. Materials and methods: In this study, the IC50 of 5-Azacitidine was first determined by the MTT method, and after the treatment of the cells with the optimum dose, at intervals of 12, 24 and 48 hours after the treatment, the RNA of the cells was extracted. And the expression level of MDR1 and MRP1 genes was measured by Real Time PCR method. Result: Treatment of cells with Azacitidine caused a significant increase in the MRP1 gene and a non-significant decrease in the MDR1 gene at 12 and 24 hours after treatment and a non-significant increase of the same gene at 48 hours after treatment.