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

Zhongguo Yao Li Xue Bao. 1995 Jul;16(4):333-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antineoplastic Agents / pharmacology*
  • DNA Topoisomerases, Type II / biosynthesis
  • Doxorubicin / pharmacology*
  • Drug Resistance, Multiple / genetics*
  • Gene Expression
  • Glutathione Transferase / metabolism
  • Humans
  • Leukemia, Erythroblastic, Acute / genetics
  • Leukemia, Erythroblastic, Acute / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Cells, Cultured / drug effects


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • RNA, Messenger
  • Doxorubicin
  • Glutathione Transferase
  • DNA Topoisomerases, Type II