Cross-resistance to cytosine arabinoside in human acute myeloid leukemia cells selected for resistance to vincristine

Exp Oncol. 2006 Jun;28(2):163-5.

Abstract

Aim: The goals of the study were to reveal the involvement of P-glycoprotein (P-gp), the product of multidrug resistance 1 gene (MDR1) in cellular resistance to vincristine (VCR) and investigate cross-resistance against cytosine arabinoside (Ara-C) in HL60 and HL60/VCR cell lines.

Methods: HL60 cells (human acute myeloid leukemia cell line) were cultured on medium with 1-50 nM of VCR for 4-6 weeks, and VCR resistant cells (HL60/VCR) were selected. The viability of cells was assessed by MTT assay and the expression of MDR1 gene was detected by RT-PCR.

Results: No expression of MDR1 gene was revealed in HL60 cells, but MDR1 started to be expressed after incubation of cells with 2 nM of VCR and its expression level elevates with increase of agent concentration. MTT test has shown that HL-60/VCR cells were 75-fold more resistant to VCR and 42-fold higher resistant to cytosine arabinoside (Ara-C) compared to sensitive HL60 cells.

Conclusion: Aquired resistance to VCR and cross-resistance to Ara-C correlates with MDR1 gene expression in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Acute Disease
  • Antineoplastic Agents / pharmacology*
  • Cytarabine / pharmacology*
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression
  • Humans
  • Leukemia, Myeloid / genetics*
  • Selection, Genetic
  • Tumor Cells, Cultured
  • Vincristine / pharmacology*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Cytarabine
  • Vincristine