Abstract
Arg-Gly-Asp (RGD) amino acid sequence was originally found in fibronectin, a main component of extracellular matrices, and is known as a ligand to some adhesion molecules. Synthetic peptides based on the sequence have been found to decrease metastatic colonization of metastatic tumors. To attempt stabilization and prolong the circulation time of a compound having RGD sequence, an RGD mimetic (arginyl-aminohexanoic acid, NOK) and its hydrophobized derivative (NOK-L) were synthesized. At first, the effect of NOK and liposomal NOK-L on adhesion properties of tumor cells in vitro was investigated. NOK inhibited adhesion of B 16 BL 6 murine melanoma cells to immobilized NOK-L. Liposomal NOK-L inhibited adhesion of the cells to fibronectin, suggesting that NOR mimic the function of RGD, Next, we investigated the metastasis-suppressing efficacy of NOK and liposomal NOK-L in vivo, using the models of both experimental and spontaneous metastasis of B 16 BL 6 cells. As a result, a significant decrease in lung colonization was observed in a group injected with liposomal NOK-L in both models. These results indicate that NOR has the metastasis-suppressing activity via the mechanism similar to that by RGD, and that liposomalization of NOK using NOK-L augmented the metastasis-suppressing activity. Thus, liposomal NOK may be useful as an antimetastatic agent.
