STI571 enhances the effect of arsenic trioxide and Velcade on bcr/abl+-CD34+ cell proliferation and apoptosis.
- Author:
Cheng-yu LI
1
;
Fan-yi MENG
;
Qi-xin SUN
;
Yun-bi FU
;
Li LI
;
Zheng-shan YI
;
Lan-lin SONG
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Aged; Apoptosis; drug effects; Arsenicals; pharmacology; Benzamides; Boronic Acids; pharmacology; Bortezomib; Cell Proliferation; drug effects; Drug Synergism; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; pathology; Middle Aged; Oxides; pharmacology; Piperazines; pharmacology; Pyrazines; pharmacology; Pyrimidines; pharmacology; Tumor Cells, Cultured
- From: Journal of Southern Medical University 2007;27(11):1665-1669
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSbcr/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.
RESULTSLow-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.
CONCLUSIONCombination with STI571 enhances the effects of As2O3 and Velcade on bcr/abl+-CD34+ cells, suggesting the potential clinical value of this regimen.
