Characterization of a human myeloid leukemia cell line highly resistant to taxol

Leukemia. 1994 Mar;8(3):465-75.


Taxol-resistant sublines of HL-60 myeloid leukemia cells (HL-60/TAX100 and HL-60/TAX1000) have been isolated in vitro by subculturing in progressively higher concentrations of taxol. HL-60/TAX100 and HL-60/TAX1000 cells are capable of continuous growth in the presence of 0.1 microM and 1.0 microM taxol, respectively, and the IC50 (50% growth inhibitory dose) values for taxol for the two sublines are 0.34 and 2.44 microM as compared to 3.1 nM for the parent HL-60 cells. HL-60/TAX100 and HL-60/TAX1000 cells display a variable degree of cross-resistance to taxotere, vincristine and doxorubicin, but are sensitive to the antimetabolite Ara-C. Both HL-60/TAX100 and HL-60/TAX1000 cells over-express MDR-1 m-RNA and the membrane efflux multidrug transporter P-glycoprotein (PGP), as determined by Western blot and immunofluorescence labeling with anti-PGP antibodies. Consequently, exposure of the taxol-resistant cells to [3H]taxol or daunomycin results in the accumulation of significantly lower levels of the two drugs. Co-treatment with cyclosporine (0.5 microgram/ml) or verapamil (10 microM) partially overcomes taxol resistance in HL-60/TAX1000 cells. Following treatment with clinically relevant concentration of taxol (1.0 microM for 24 h), HL-60 but not HL-60/TAX1000 cells display intracellular microtubular bundling, markedly enhanced accumulation of the cells in G2/M phase of cell-cycle and internucleosomal DNA fragmentation associated with apoptosis which is independent of bcl-2 gene expression. These taxol-resistant myeloid leukemia cells may serve as in vitro experimental models for examinating strategies which may have potential applicability for overcoming taxol resistance.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Apoptosis / drug effects
  • Carrier Proteins / analysis
  • Carrier Proteins / genetics
  • Cell Division / drug effects
  • Cyclosporine / pharmacology
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / drug effects
  • Daunorubicin / pharmacokinetics
  • Drug Resistance / genetics
  • Humans
  • Leukemia, Myeloid / drug therapy
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / pathology*
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / genetics
  • Microtubules / drug effects
  • Microtubules / ultrastructure
  • Paclitaxel / pharmacokinetics
  • Paclitaxel / pharmacology*
  • Tumor Cells, Cultured
  • Verapamil / pharmacology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Carrier Proteins
  • DNA, Neoplasm
  • Membrane Glycoproteins
  • Cyclosporine
  • Verapamil
  • Paclitaxel
  • Daunorubicin