| Abstract: | Various retinoids and interferons exert anti-tumor effects both in experimental studies and in clinical trials. Recent reports indicate that they have a synergistic antineoplastic activity. Our study aimed to determine whether these synergistic anti-tumor effects are related to inhibition of tumor-cell-induced angiogenesis. A further aim was to compare the anti-angiogenic activity of various retinoids including 9-cis retinoic acid, a ligand for nuclear retinoic acid receptor RXR, given alone and in combination with interferon α-2a (IFNα-2a). An in vivo experimental model of cutaneous angiogenesis in the mouse was used. Angiogenesis was induced by intradermal injection of HPVI6-or HPVI8 DNA-harboring tumor-cell lines. All-trom retinoic acid (all-trans RA), 13-cis retinoic acid (13-cis RA) and 9-cis retinoic acid (9-cis RA) as well as 1FNα-2a applied to mice intra-peritoneally for S consecutive days before induction of angiogen-esis resulted in significant inhibition of angiogenesis. Combination of retinoids with IFNα-2a led to a synergistic inhibition of angiogenesis, as compared to the effects of the drugs given alone. Similar results were obtained when tumor cells were preincubated in vitro with the compounds, before injection into untreated mice. Our findings on synergistic anti-angiogenic effects of retinoids and IFNα-2a could explain, at least partially, the anti-tumor efficacy of combined therapy with these agents, and provide support for the role of angiogenesis in tumor growth. © Wiley-Liss, Inc. |
