[STI571 enhances the effect of arsenic trioxide and Velcade on bcr/abl+-CD34+ cell proliferation and apoptosis].
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.
Li
Cheng-yu
CY
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. davidlee556762@163.com
Meng
Fan-yi
FY
Sun
Qi-xin
QX
Fu
Yun-bi
YB
Li
Li
L
Yi
Zheng-shan
ZS
Song
Lan-lin
LL
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
D001152:Arsenicals; D001549:Benzamides; D001897:Boronic Acids; D010087:Oxides; D010879:Piperazines; D011719:Pyrazines; D011743:Pyrimidines; D000069286:Bortezomib; D000068877:Imatinib Mesylate; D000077237:Arsenic Trioxide