Interferon alpha 2b inhibits the murine melanoma cell line Cloudman S91 invivo but not in vitro: A model for studying tumor cell-cytokine interactions

Interferon alpha 2b has recently been shown to improve outcome in patients with metastatic malignant melanoma. The high-dose interferon therapy used i s however associated with significant systemic adverse effects. These adver se effects are likely related to the multitude of actions of interferon whi ch in addition to its antineoplastic effects also possesses antiviral and i mmunomodulating properties. Elucidation of the mechanism of the antiprolife rative effects of interferon may allow for the development of agents that p ossess the antineoplastic properties while being devoid of the other effect s that make interferon toxic. In the animal model developed for this study tumors in mice receiving interferon alpha 2b grew at a slower rate and achi eved a small final tumor volume (3040 +/- 690 vs 1400 +/- 314 mm(3) for the control and treated groups respectively, P < 0.05). Furthermore the final tumor weight in the treated group was significantly smaller (1.50 +/- 0.21 g vs 2.76 +/- 0.46 g for the treated and control groups respectively; P = 0 .036). The (3-[4,5-Dimethylthiazol-2-y]-2,5-diphenyltetrazolium bromide) (M TT) colorimetric assay failed to reveal any direct effects of interferon <a lpha>2b on this murine melanoma cell line. This antiproliferative effect of interferon alpha 2b was in addition found to be independent of alterations in the expression of the angiogenic cytokines vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor beta .