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Multidrug resistance in leukemic cell line K562/A02 induced by doxorubicin
C Z Yang1, F J Luan, D S Xiong
1Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin.
Aim:
To study the mechanism of the development of multidrug resistance in leukemic cells.
Methods:
A human leukemic cell line K562/A02 was established by stepwise increase of concentrations of doxorubicin (Dox) in medium. P-glycoprotein was detected by immunohistochemistry assay. The mdr1 gene expression was measured by RT-PCR. The amplification of mdr1 gene in its genome, and DNA topisomerase II (Top II) gene expression were determined by dot-blot hybridization.
Results:
K562/A02 was highly cross-resistant to vincristine (VCR), homoharringtonin (HHT), amsacrine (m-AMSA), daunorubicin (Dau) and etoposide (VP-16), slightly to cytosine arabinoside (Ara-C), but not cisplatin (Cis), methotrexate (MTX) and fluorouracil (5-FU), showing a typical phenotype of MDR. Intracellular accumulation of Dau in K562/A02 was 33% as high as that in K562. P-glycoprotein P-170 was positive. In K562/A02, the mdr1 gene did not amplify, the mdr1 mRNA level was markedly higher, the Top II mRNA level was lower, and glutathione-S-transferase (GST) activity was higher than in K562.
Conclusion:
mdr1 mRNA was overexpression and thus the encoded P-170 was responsible for MDR in K562/A02 while Top II or GST may play a role in MDR.