[Synergistic inhibitory effect of STI571 in combination with arsenic trioxide on a multidrug-resistant leukemia cell line expressing bcr-abl].
OBJECTIVE
To 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.


METHODS
The 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.


RESULTS
The 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.


CONCLUSIONS
Combination of STI571 with As(2)O(3) has a synergistic inhibiting effect on leukemia cells expressing bcr-abl and mdr1.
Chen
Li
L
Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. yuhe0628@yahoo.com.cn
Wang
Jian-min
JM
Xu
Xiao-ping
XP
Gao
Lei
L
Fei
Xin-hong
XH
Lou
Jing-wei
JW
Huang
Zheng-xia
ZX
D000970:Antineoplastic Agents / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001549:Benzamides; D002470:Cell Survival / Q000187:drug effects*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D019450:Genes, MDR; D016313:Genes, abl; D006801:Humans; D000068877:Imatinib Mesylate; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D010087:Oxides / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology*; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D001152:Arsenicals; D001549:Benzamides; D010087:Oxides; D010879:Piperazines; D011743:Pyrimidines; D014750:Vincristine; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D000077237:Arsenic Trioxide