Premium
The effects of proteasome inhibitor bortezomib on a P‐gp positive leukemia cell line K562/A02
Author(s) -
LÜ S.,
CHEN Z.,
YANG J.,
CHEN L.,
ZHOU H.,
XU X.,
LI J.,
HAN F.,
WANG J.
Publication year - 2010
Publication title -
international journal of laboratory hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.705
H-Index - 55
eISSN - 1751-553X
pISSN - 1751-5521
DOI - 10.1111/j.1751-553x.2009.01145.x
Subject(s) - bortezomib , daunorubicin , k562 cells , leukemia , proteasome inhibitor , pharmacology , apoptosis , chemistry , cancer research , medicine , multiple myeloma , biochemistry
Summary The aim of this study is to clarify the efficacy of proteasome inhibitor bortezomib to multidrug resistant (MDR) acute leukemia cells. We observed the effects of bortezomib on a P‐glycoprotein (P‐gp) positive leukemia line K562/A02. The results showed that bortezomib has significant effects on P‐gp positive K562/A02 cells including cytotoxicity (48 h IC 50 : 171.36 n m ), induction of apoptosis (31.71 ± 1.07% apoptotic cells after 24 h treatment at 100 n m ), and inhibition of proteasome chymotrypsin‐like activity (relative activity to untreated controls: 20.07 ± 0.66% at 24 h with 10 n m bortezomib). These effects were lower than those observed in K562 cells (IC 50 , percentage of apoptotic cells, relative chymotrypsin‐like activity to untreated controls were 56.28 n m , 77.95 ± 0.35%, 5.35 ± 2.05% after the same treatments, respectively). No synergy between daunorubicin and bortezomib was shown in the killing of K562/A02 cells (synergistic ratios were <1). P‐gp expression levels did not decrease in K562/A02 cells after bortezomib treatment. Pretreatment with bortezomib does not improve the intracellular anthracycline concentration in K562/A02 cells. Bortezomib shows a promising effect for the treatment of refractory/relapsed leukemia, but it does not improve the effect of anthracycline to MDR leukemia cells.