Multidrug resistance in leukemic cell line K562/A02 induced by doxorubicin.
OBJECTIVE
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.


CONCLUSIONS
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.
Yang
C Z
CZ
Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin.
Luan
F J
FJ
Xiong
D S
DS
Liu
B R
BR
Xu
Y F
YF
Gu
K S
KS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015870:Gene Expression; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D004317:Doxorubicin; D005982:Glutathione Transferase; D004250:DNA Topoisomerases, Type II