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The aim of this study is to clarify the efficacy of proteasome inhibitor bortezomib to multidrug resistant (MDR) acute leukemia cells. We observed the effects of bortezomib on a P-glycoprotein (P-gp) positive leukemia line K562/A02. The results showed that bortezomib has significant effects on P-gp positive K562/A02 cells including cytotoxicity (48 h IC(50): 171.36 nM), induction of apoptosis (31.71 +/- 1.07% apoptotic cells after 24 h treatment at 100 nM), and inhibition of proteasome chymotrypsin-like activity (relative activity to untreated controls: 20.07 +/- 0.66% at 24 h with 10 nM bortezomib). These effects were lower than those observed in K562 cells (IC(50), percentage of apoptotic cells, relative chymotrypsin-like activity to untreated controls were 56.28 nM, 77.95 +/- 0.35%, 5.35 +/- 2.05% after the same treatments, respectively). No synergy between daunorubicin and bortezomib was shown in the killing of K562/A02 cells (synergistic ratios were <1). P-gp expression levels did not decrease in K562/A02 cells after bortezomib treatment. Pretreatment with bortezomib does not improve the intracellular anthracycline concentration in K562/A02 cells. Bortezomib shows a promising effect for the treatment of refractory/relapsed leukemia, but it does not improve the effect of anthracycline to MDR leukemia cells.

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