The Study of Bortezomib Alone or in Combination with Harringtonine or Arsenic Trioxide on Proliferation and Apoptosis of Multidrug Resistant Leukemic Cells.

To investigate the effect of bortezomib alone or combined with harringtonine (HT) or arsenic trioxide (As₂O₃) on the proliferation activity and apoptosis of HL60/ADM cell line and refractory/relapse acute leukemia primary cell. HL60/ADM cells or refractory/relapse acute leukemia primary cells were incubated with bortezomib at different doses alone and in combination with HT or As₂O₃. The proliferation activity was abserved by MTT assay, cell apoptosis was studied by fluorescence microscopy and flow cytometry. Intracellular concentration of daunorubicin (DNR) was determined by flow cytometry. In bortezomib-treated tumor cells, inhibition rate enhanced and apoptotic cells increased in mumber time- and dose-dependently. 40nM Bortezomib can best inhibit the proliferation activity of HL60/ADM cells when incubated for 48 hours. 15uM As₂O₃ or 752nM HT combined with different doses of bortezomib can inhibit the proliferation and induce the apoptosis of HL60/ADM cells, The dual inhibition of As₂O₃ plus bortezomib or HT plus bortezomib may present a superior anticancer efficancy to either inhibition of the drugs above alone (P<0.05;<0.01). Bortezomib (10nM) can markedly enhance the intraceflular accumulation of DNR in HL60/ADM cells(P=0.000). Bortezomib can inhibits proliferation and induces apoptosis of HL60/ADM cells and refactory/ relapse acute leukemic primary cells. When combined with HT or As₂O₃ appear to have synergistic effects, and the mechanisms might be associated with the ability of reversing multidrug resisitant of Bortezomib.