ram, an rgds analog, exerts potent anti-melanoma effects in vitro and in vivoram、rgds模拟施加强有力的anti-melanoma影响体外和体内.pdfVIP

RAM, an RGDS Analog, Exerts Potent Anti-Melanoma Effects In Vitro and In Vivo 1 1 2 1 Maria Simona Aguzzi , Daniela D’Arcangelo , Claudia Giampietri , Maurizio C. Capogrossi , Antonio Facchiano1* 1 Laboratorio Patologia Vascolare, Istituto Dermopatico dell’Immacolata, IDI-IRCCS, Rome, Italy, 2 D.A.H.F.M.O. Section of Histology Medical Embryology, Sapienza University of Rome, Rome, Italy Abstract Peptides containing the RGD sequence are under continuous investigation given their ability to control cell adhesion and apoptosis. Since small peptides are quickly metabolized and degraded in vivo, developing analogs resistant to serum- induced degradation is a challenging task. RGD analogs developed so far are known as molecules mostly inhibiting cell adhesion; this feature may reduce cell proliferation and tumor development but may not induce regression of tumors or metastases already formed. In the current study, carried out in melanoma in vitro and in vivo models, we show that RAM, an RGD-non-peptide Analog-Molecule, strongly inhibits cells adhesion onto plastic, vitronectin, fibronectin, laminin and von Willebrand Factor while it does not inhibit cell adhesion onto collagen IV, similarly to the RGDS template peptide. It also strongly inhibits in vitro cell proliferation, migration and DNA-synthesis, increases melanoma cells apoptosis and reduces survivin expression. All such effects were observed in collagen IV seeded cells, therefore are most likely independent from the anti adhesive properties. Further, RAM is more stable than the template RGDS; in fact it maintains its anti-proliferation and anti-adhesion effects after long serum exposure while RGDS almost completely loses its effects upon serum exposure. In a