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Keywords:

  • Proteasome inhibitor;
  • bortezomib;
  • P-gp;
  • leukemia

Summary

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 IC50: 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 (IC50, 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.