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 growth, apoptosis and the production of vascular endothelial growth factor (VEGF) was investigated in the human melanoma cell line IGR 1. We determined cell proliferation, cell vitality, DNA synthesis, apoptosis, intracellular oxygen radicals (ROS) and VEGF-mRNA as well as VEGF-protein levels. rIFN-gamma significantly inhibited growth by decreasing DNA synthesis and increasing apoptosis. Less pronounced was the growth inhibitory effect of nIFN-beta because an increased rate of apoptosis was outweighed by enhanced DNA synthesis. nIFN-alpha only had minor effects on cell growth parameters. Under long-term incubation (144 h) nIFN-beta decreased, but rIFN-gamma increased production of the angiogen VEGF. Our data underscore the multiple effects of IFNs on melanoma cells and may contribute to the understanding of ambivalent results of melanoma therapy by IFNs. Particularly, the increased VEGF production under long-term treatment with serum IFN levels between 100 and 1,200 IU/ml should be kept in mind.
Bölling
B
B
Max Planck Institut für molekulare Physiologie, Dortmund, Germany.
Fandrey
J
J
Frosch
P J
PJ
Acker
H
H
D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D016898:Interferon-alpha; D008222:Lymphokines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016899:Interferon-beta; D007371:Interferon-gamma; D004247:DNA