Overcoming of vincristine resistance in HL-60 human promyelocytic leukemia cell line by dipyridamole.
Dipyridamole enhanced the anti-cancer activity of VCR toward both wild type HL-60 and VCR-resistant subline, HL-60/R, which had a 15 fold greater resistance to VCR as compared with the wild type cell line. The resistance to VCR of HL-60/R cells was associated with a marked decrease in the intracellular VCR accumulation. After incubation with VCR for 24 hrs, 0.61 and 0.24 pmol VCR per one million cells were accumulated in the wild and the resistant cells, respectively. Dipyridamole dose-dependently increased the intracellular VCR accumulation in the wild type cells and also it restored the intracellular VCR accumulation in the VCR-resistant cells. Addition of 10 microM dipyridamole to the culture medium enhanced the intracellular accumulation of VCR during 24 hr incubation by 2.6 fold and 6.0 fold in HL-60 and HL-60/R cells, respectively. The VCR-resistance in HL-60/R cells was able to be overcome by the addition of 2.5 microM dipyridamole to the culture medium. This concentration of dipyridamole could be obtained by the intravenous administration without severe adverse effects. These results indicate that dipyridamole should be effective in the treatment of patients with hematologic malignancy resistant to VCR.
Hirose
M
M
Division of Blood Transfusion, School of Medicine, University of Tokushima, Japan.
Takeda
E
E
Kuroda
Y
Y
D004176:Dipyridamole / Q000008:administration & dosage; D004351:Drug Resistance; D004357:Drug Synergism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014750:Vincristine / Q000008:administration & dosage / Q000494:pharmacology*
D014750:Vincristine; D004176:Dipyridamole