Synergistic inhibitory effect of STI571 in combination with arsenic trioxide on a multidrug-resistant leukemia cell line expressing bcr-abl.
- Author:
Li CHEN
1
;
Jian-min WANG
;
Xiao-ping XU
;
Lei GAO
;
Xin-hong FEI
;
Jing-wei LOU
;
Zheng-xia HUANG
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; pharmacology; Arsenicals; pharmacology; Benzamides; Cell Survival; drug effects; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Genes, MDR; Genes, abl; Humans; Imatinib Mesylate; Inhibitory Concentration 50; K562 Cells; Oxides; pharmacology; Piperazines; pharmacology; Protein-Tyrosine Kinases; antagonists & inhibitors; Pyrimidines; pharmacology; Vincristine; pharmacology
- From: Chinese Journal of Oncology 2004;26(9):535-538
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the synergistic effect of STI571, an inhibitor of tyrosine kinase in combination with arsenic trioxide (As(2)O(3)) on a multidrug-resistant leukemia cell line expressing bcr-abl.
METHODSThe cytotoxic effect of STI571 alone or in combination with different concentrations of As(2)O(3) on both bcr-abl and mdr1 positive leukemia cell line K562-n/VCR was detected by MTT method.
RESULTSThe cytotoxic effect of STI571 (1 micromol/L) combined with As(2)O(3) at concentrations 10(-5), 10(-6), 10(-7), 10(-8) mol/L (IC(50) 0.155 micromol/L) on K562-n/VCR cells was significantly higher than that of As(2)O(3) alone (IC(50) 1.879 micromol/L). The synergistic interaction on K562-n/VCR cells increased the cytotoxic effect by 12.1-fold.
CONCLUSIONCombination of STI571 with As(2)O(3) has a synergistic inhibiting effect on leukemia cells expressing bcr-abl and mdr1.