Interleukin 3 enhances the cytotoxic activity of 1-beta-D-arabinofuranosylcytosine (ara-C) on acute myeloblastic leukaemia (AML) cells.
We have evaluated the possibility of enhancing the cell killing effect of ara-C on AML blasts by increasing their proliferative activity with haemopoietic growth factors. Leukaemic cells from 10 AML patients were incubated for 3 d in liquid culture in the presence or in the absence of the human recombinant growth factors IL-1 beta (5 U/ml) and IL-3 (3 U/ml), and subsequently exposed to ara-C (3 micrograms/ml) for the last 24 h. The number of residual leukaemic stem cells was evaluated by a clonogenic assay in semisolid medium. The results showed that ara-C exposure inhibits the proliferation of a higher proportion of clonogenic cells in cultures pretreated with growth factors than in the controls (mean inhibitory values: in the absence of growth factors = 49.8%; with IL-1 beta = 58.3%; with IL-3 78.9%). The effect was statistically significant only when IL-3 was used as a growth factor. The results suggest that haemopoietic growth factors may help to improve the therapeutic index of cytostatic agents.
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Istituto di Medicina Interna dell'Università di Torino, Italy.
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Avanzi
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D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007375:Interleukin-1; D007377:Interleukin-3; D003561:Cytarabine