VEGF production, cell proliferation and apoptosis of human IGR 1 melanoma cells under nIFN-alpha/beta and rIFN-gamma treatment

The effect of natural and recombinant interferons (nIFN, rIFN) on cell grow th, apoptosis and the production of vascular endothelial growth factor (VEG F) was investigated in the human melanoma cell line IGR 1. We determined ce ll proliferation, cell vitality, DNA synthesis, apoptosis, intracellular ox ygen radicals (ROS) and VEGF-mRNA as well as VEGF-protein levels, rIFN-gamm a significantly inhibited growth by decreasing DNA synthesis and increasing apoptosis. Less pronounced was the growth inhibitory effect of nIFN-beta b ecause an increased rate of apoptosis was outweighed by enhanced DNA synthe sis. nIFN-alpha only had minor effects on cell growth parameters. Under lon g-term incubation (144 h) nIFN-beta decreased, but rIFN-gamma increased pro duction of the angiogen VEGF. Our data underscore the multiple effects of I FNs on melanoma cells and may contribute to the understanding of ambivalent results of melanoma therapy by IFNs. Particularly, the increased VEGF prod uction under long-term treatment with serum IFN levels between 100 and 1200 IU/ml should be kept in mind.