Increased survival rate in acute lymphoblastic leukemia treated with methotrexate by DR5 and Caspase-8 in hyperglycemic conditions

Background and Aims: Considering the drug resistance of chemotherapy in diabetic patients and the prevalence of acute lymphoblastic leukemia in them, the present study aimed to investigate the effect of hyperglucose condition on the expression of DR5 and Caspase-8 genes in lymphoblastic cells (NALM-6) and its relationship to the cells' response to methotrexate. Materials and Methods:In this in vitro study, NALM-6 cells were cultured in RPMI 1640 medium with 10% fetal bovine serum (FBS) containing antibiotics across four control groups: cells in the control group (C), cells treated with methotrexate (C+M), cells treated in an environment with high glucose concentration (G), and cells treated in an environment with high glucose concentration and methotrexate (G+M).The treated cells were subjected to hyperglucose conditions for 10 days in an environment with high glucose concentration.The survival rate of methotrexate-treated cells was evaluated by the MTT method, and then the relative expression of DR5 and Caspase-8 genes was measured by the RT-qPCR method.The statistical significance was defined as a P-value less than 0.05. Results:The M group had 50% survival compared to the control group, and the G+M group had 58% survival compared to the control group.The expression of the DR5 gene in the group G+M compared to the G group was not significantly different (P>0.05);however, the expression of the caspase-8 gene in the G group was significantly lower compared to the control group (P<0.01) and also lower in the G group compared to the treated cells (P<0.001). Conclusion:The findings indicated that the survival rate of NALM-6 cells in high concentrations of glucose after treatment with methotrexate was higher than the same condition in the control group, which indicates the effect of glucose resistance on drug treatment.