Differential Resistance of Melanoma Cells to Treatment with Recombinant IFN-α2b and Leukocyte IFN

Abstract

Background: Interferon-α (IFN-α) subtypes bind to the same receptor and are expected to have the same biological functions. Whether or not leukocyte IFN, containing six major IFN-α proteins had the same anti-tumor effect as one subtype, recombinant IFN-α2b, 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-α2b 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-α as compared to IFN-α2b.