Recombinant human granulocyte colony-stimulating factor enhanced cytotoxicity of Ara-C in Ara-C-resistant leukemic cells from a patient with biphenotypic leukemia in cell kinetic quiescence.
In vitro preincubation with recombinant granulocyte colony-stimulating factor(rhG-CSF, 100 ng/ml) enhanced the cytotoxicity of 1-beta-D-arabinofuranosylcytosine(Ara-C) in leukemic cells resistant to Ara-C from a patient with biphenotypic leukemia. Treatment of the cells with rhG-CSF resulted in a 17-fold increase in DNA synthesis, 4.6-fold increase in percentage of S-phase, and a two-fold increase in Ara-CTP formation. Maximal effect was observed at 72 h of incubation. Combination chemotherapy with rhG-CSF and Ara-C to the patient showed remarkable cytoreduction. These results indicate that recruitment of resistant leukemic cells in cell kinetic quiescence is inducible by rhG-CSF and that it is possible enhancement of the cytotoxicity to cell cycle-specific drugs such as Ara-C.
Higashigawa
M
M
Department of Pediatrics, Mie University School of Medicine, Japan.
Komada
Y
Y
Washio
N
N
Kuwabara
H
H
Hori
H
H
Ido
M
M
Sakurai
M
M
D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002648:Child; D003561:Cytarabine / Q000494:pharmacology*; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D014316:Tritium; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D003561:Cytarabine; D014316:Tritium; D016179:Granulocyte Colony-Stimulating Factor; D004247:DNA