Differential resistance of melanoma cells to treatment with recombinant IFN-alpha2b and leukocyte IFN.

• BACKGROUND: Interferon-alpha (IFN-alpha) subtypes bind to the same receptor and are expected to have the same biological functions. Whether or not leukocyte IFN, containing six major IFN-alpha proteins had the same anti-tumor effect as one subtype, recombinant IFN-alpha2b, was investigated. MATERIALS AND METHODS: Three melanoma lines were treated with both types of IFN, and the effect on proliferation and survival was estimated both after short-term and prolonged treatment. RESULTS: All the melanoma cell lines were sensitive to the antiproliferative effects of both IFN species during short-term treatment. However, upon prolonged culture, the frequency of resistant colony formation was significantly higher in cultures treated with IFN-alpha2b compared to those treated with leukocyte IFN. There was a qualitative difference between the resistant colonies selected by the two IFN species with respect to morphology, growth rate and sensitivity to apoptosis. CONCLUSION: The development of resistant clones occurred at a lower rate during long-term treatment with leukocyte IFN containing six major subtypes of IFN-alpha as compared to IFN-alpha2b.

Nyckelord

Antineoplastic Agents/*pharmacology

Cell Growth Processes/drug effects

Drug Resistance; Neoplasm

Humans

Interferon Alfa-2b/*pharmacology

Interferon-alpha/*pharmacology

Melanoma/*drug therapy/pathology

Tumor Cells; Cultured

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