A NEW PSEUDO-PEPTIDE ANALOG OF THE ARG-GLY-ASP (RGD) SEQUENCE INHIBITS LIVER METASTASIS OF COLON 26-L5 CARCINOMA-CELLS

We have investigated the effect of the pseudo-peptide analogue (FC-336 ) of the Arg-Gly-Asp (RGD) sequence in a liver metastasis model by the inoculation of a highly liver-metastatic cell line of colon 26 carcin oma (colon 26-L5) into the portal vein of BALB/c mice. The intraportal injection of colon 26-L5 cells with FC-336 resulted in a marked suppr ession of liver metastatic colonies in a dose-dependent manner and it reduced the liver weights to a normal level. However, the co-injection of tumor cells with a high dose of RGDS tetrapeptide led to a slight inhibition of liver metastasis. The multiple i.v. administration of FC -336 after tumor inoculation as well as the injection of FC-336 with t umor cells caused significant inhibition of experimental metastasis in the liver. The multiple i.v. administration of the RGDS peptide did n ot show any inhibitory activity. FC-336 significantly enhanced the sur vival rate of mice compared with untreated controls when injected intr aportally with tumor cells or when intravenously administered after tu mor inoculation. Zymography analysis showed that FC-336 inhibited the degradation of gelatin substrate by matrix metalloproteinases (MMPs) p roduced by colon 26-L5 cells, while RGDS peptide did not affect the en zymatic degradation. These findings clearly indicate that the pseudo-p eptides of the RGD sequence (FC-336) have a potent inhibitory activity on liver metastasis of colon 26-L5 carcinoma cells. (C) 1998 Elsevier Science Ireland Ltd.