Objective: To study the effects of STI571, arsenic trioxide (As2O3) and Velcade, used alone or in combination, on the proliferation and apoptosis of bcr/abl+-CD34+ cells.
Methods: bcr/abl+-CD34+ cells isolated from the bone marrow of patients with chronic myeloid leukemia (CML) were treated for 96 h with STI571, As2O3 and Velcade either alone and in combination, and the cell proliferation and apoptosis were analyzed by CCK-8 assay and flow cytometry. The morphological changes of the apoptotic cells were observed by Hoechst33342 staining and fluorescent microscope. The inhibitory effects of the drugs on normal CD34+ cells were also observed.
Results: Low-concentration STI571, As2O3 or Velcade all dose-dependently inhibited bcr/abl+-CD34+ cell proliferation without obvious apoptosis-inducing effects. STI571 at 0.25-2 micromol/L combined with As2O3 at 2.5 micromol/L and with Velcade at 15 nmol/L both significantly increased the cell inhibition and apoptosis rates, showing obvious additive or synergistic effects of the drugs without further enhancement of normal CD34+ cell inhibition.
Conclusion: Combination with STI571 enhances the effects of As2O3 and Velcade on bcr/abl+-CD34+ cells, suggesting the potential clinical value of this regimen.