A new pseudo-peptide analogue of the Arg-Gly-Asp (RGD) sequence inhibits liver metastasis of colon 26-L5 carcinoma cells.

Abstract

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 carcinoma (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 suppression 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 tumor cells caused significant inhibition of experimental metastasis in the liver. The multiple i.v. administration of the RGDS peptide did not show any inhibitory activity. FC-336 significantly enhanced the survival rate of mice compared with untreated controls when injected intraportally with tumor cells or when intravenously administered after tumor inoculation. Zymography analysis showed that FC-336 inhibited the degradation of gelatin substrate by matrix metalloproteinases (MMPs) produced by colon 26-L5 cells, while RGDS peptide did not affect the enzymatic degradation. These findings clearly indicate that the pseudo-peptides of the RGD sequence (FC-336) have a potent inhibitory activity on liver metastasis of colon 26-L5 carcinoma cells.

• Authors: Y Ohnishi, H Fujii, K Murakami, T Sakamoto, K Tsukada, M Fujimaki, M Kojima, I Saiki
• Journal: Cancer letters (Cancer Lett) Vol. 124 Issue 2 Pg. 157-63 (Feb 27 1998) ISSN: 0304-3835 [Print] Ireland
• PMID: 9500205 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Oligopeptides
• arginyl-glycyl-aspartic acid
• arginyl-glycyl-aspartyl-serine
• Collagenases
• Metalloendopeptidases
• Matrix Metalloproteinase 9

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Collagenases (drug effects, metabolism)
• Colonic Neoplasms (drug therapy, enzymology, pathology)
• Female
• Liver Neoplasms, Experimental (enzymology, prevention & control, secondary)
• Matrix Metalloproteinase 9
• Metalloendopeptidases (metabolism)
• Mice
• Mice, Inbred BALB C
• Oligopeptides (therapeutic use)