Abstract:

Abstract:Objective To investigate the reversal effect of a novel polyamine conjugate,NMMB,on multidrug resistance (MDR) of myelogenous leukemia K562/ADM cells and  discuss the possible correlative mechanism.Methods K562 and K562/ADM cells in culture medium were treated with NMMB (10-1 000 mg/L) respectively.The inhibitory rates of these cells were measured by MTT assay.Non-cytotoxic dose of NMMB was determined. K562/ADM cells at logarithmic growth phase were randomly divided into ADM control,NMMB 2.5,5.0,10.0 mg/L groups.The inhibitory rate 50% (IC50) and the reversal index in all groups were determined.The effects of NMMB on ADM accumulation in K562/ADM cells and cell cycle  were examined by flow cytometry (FCM).Results The inhibitory rates were significantly increased when the cells were treated with different doses of NMMB (10-1 000 mg/L) in a dose-dependent manner.The available reversal concentration of NMMB was 12.5 mg/Land the reversal index was 4 folds on K562/ADM cells.ADM accumulation in K562/ADM cells was significantly increased (P<0.05).The cells were blocked at the period of G0/G1 (P<0.01).Conclusion NMMB has an effect on proliferation inhibition and MDR reversal of K562/ADM cell line.The reversal mechanisms of   NMMB may be due to increasing the accumulation of chemo-drugs in cells and arresting the cells at 0/G1 phase.

Key words: polyamines conjugate;multi-drug resistance;reversal of drug resistance;K562/ADM cell