title: [STI571 enhances the effect of arsenic trioxide and Velcade on bcr/abl+-CD34+ cell proliferation and apoptosis].
abstract: 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.
  
  
  CONCLUSIONS
  Combination with STI571 enhances the effects of As2O3 and Velcade on bcr/abl+-CD34+ cells, suggesting the potential clinical value of this regimen.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. davidlee556762@163.com
authors.forename: Cheng-yu
authors.initials: CY
authors.lastname: Li
authors.forename: Fan-yi
authors.initials: FY
authors.lastname: Meng
authors.forename: Qi-xin
authors.initials: QX
authors.lastname: Sun
authors.forename: Yun-bi
authors.initials: YB
authors.lastname: Fu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Zheng-shan
authors.initials: ZS
authors.lastname: Yi
authors.forename: Lan-lin
authors.initials: LL
authors.lastname: Song
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001549:Benzamides; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D049109:Cell Proliferation / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008875:Middle Aged; D010087:Oxides / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D001152:Arsenicals; D001549:Benzamides; D001897:Boronic Acids; D010087:Oxides; D010879:Piperazines; D011719:Pyrazines; D011743:Pyrimidines; D000069286:Bortezomib; D000068877:Imatinib Mesylate; D000077237:Arsenic Trioxide