A new pseudo-peptide analogue 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 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.
Ohnishi
Y
Y
Department of Pathogenic Biochemistry, Research Institute for Wakan-yaku, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Fujii
H
H
Murakami
K
K
Sakamoto
T
T
Tsukada
K
K
Fujimaki
M
M
Kojima
M
M
Saiki
I
I
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017364:Collagenases / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000517:prevention & control* / Q000556:secondary*; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; C046617:arginyl-glycyl-aspartyl-serine; D017364:Collagenases; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9