Synergistic Inhibition of Chronic Myeloid Leukemia: Combining Imatinib and Naringin to Overcome Drug Resistance

Chronic Myeloid Leukemia (CML) treatment with Imatinib often encounters the challenge of drug resistance, limiting its long-term efficacy. This study aimed to evaluate the cytotoxic effects and underlying mechanisms of Naringin, both alone and in combination with Imatinib, on Imatinib-sensitive (K562-S) and Imatinib-resistant (K562-R) CML cell lines. Imatinib resistance in K562 cells was induced through a stepwise exposure to the drug. Cytotoxicity was assessed using the MTT assay, while flow cytometry was employed to determine the expression levels of P-glycoprotein (P-gp), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT). Molecular docking studies were conducted to explore potential interaction mechanisms. The combination treatment significantly reduced cell viability and downregulated P-gp, ERK, and AKT expression in both cell lines, indicating a synergistic effect. These findings suggest that Naringin can potentiate the therapeutic efficacy of Imatinib, offering a promising strategy to overcome drug resistance and improve clinical outcomes in CML management.