Cyclosporine diminishes multidrug resistance in K562/ADM cells and improves complete remission in patients with acute myeloid leukemia

Abstract

This study was designed to investigate the effects of cyclosporine A (CsA) on a multidrug resistance cultured cell line, and its effect on complete remission in patients with acute myeloid leukemia (AML). A multidrug resistant K562/ADM cell line and drug-sensitive K562 cell line was used. The intracellular concentration of daunorubicin and the accumulation of Rhodamine 123 (Rh123) in the K562/ADM and K562 cells were evaluated. Clinical effects of CsA were also studied in 65 patients with AML. In the K562/ADM cells, the 50% of inhibition concentration (IC50) of daunorubicin only group was 23.0 ± 5.2 μmol/L, which was greater than in other groups co-administered with CsA (1.2 ± 4.8 μmol/L), verapamil (1.5 ± 5.4 μmol/L) or CsA + verapamil (1.4 ± 4.3 μmol/L) (all P < 0.01). The relative fluorescence intensity of Rh123 in the K562/ADM cells treated with CsA and daunorubicin was increased from 48.9% to 69.8% ( P < 0.05). CsA also improved the complete remission rate in the AML patients (72.7% vs 21.9%, P < 0.01). We conclude that CsA can significantly diminish the multidrug resistance in K562/ADM cells. It also enhances the complete remission rates in patients with AML. CsA may be used as an integral part of the chemotherapy for AML.