Modulation of in vitro chemosensitivity in acute myelogenous leukemia cell line by GM-CSF: opposing effects observed with different cytotoxic drugs and time exposure.
In some studies the GM-CSF (granulocyte-macrophage colony-stimulating factor) increased the in vitro sensitivity of acute myeloid leukemia (AML) cells to cytosine arabinoside (Ara-C), however, in clinical trials no favorable effects were shown. We used a GM-CSF responsive AML cell line (AML 193) to test the effects of growth stimulation on in vitro efficacy of Ara-C and methotrexate (MTX). In 6 days continuous exposure, dose dependent Ara-C cytotoxicity was counteracted by GM-CSF. Conversely, MTX cytotoxicity was increased significantly. However, in a short term treatment (24 h, high doses) the GM-CSF increased both MTX and Ara-C cytotoxicity. These effects might depend on different drug regimens and cell features.
Ciaiolo
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Dipartimento di Medicina e Oncologia sperimentale, Sezione di Ematologia, Ospedale Molinette, Torino, Italy. ciaiolo@yahoo.com
Ferrero
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D
Pugliese
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Ortolano
B
B
Borrione
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Pileri
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D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008727:Methotrexate / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008727:Methotrexate