title: Multidrug resistance in leukemic cell line K562/A02 induced by doxorubicin.
abstract: 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.
authors.affiliation: Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin.
authors.forename: C Z
authors.initials: CZ
authors.lastname: Yang
authors.forename: F J
authors.initials: FJ
authors.lastname: Luan
authors.forename: D S
authors.initials: DS
authors.lastname: Xiong
authors.forename: B R
authors.initials: BR
authors.lastname: Liu
authors.forename: Y F
authors.initials: YF
authors.lastname: Xu
authors.forename: K S
authors.initials: KS
authors.lastname: Gu
mesh_terms: 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
chemical_list: 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