Combination of anti-cell adhesive synthetic Arg-Gly-Asp-Ser analogue and anticancer drug doxorubicin heightens their original antimetastatic activities.

Abstract

A new compound containing the cell-adhesive Arg-Gly-Asp-Ser (RGDS) peptide was synthesized, i.e. tetrahydrofurantetracarboxylic acid (THFTCA)-RGDS conjugate [THFTCA- (RGDS)3, FC-243], and the inhibitory effect of FC-243 on lung metastasis of B16-BL6 melanoma in mice was examined in combination with or without the anticancer agent doxorubicin (DOX). FC-243 showed an inhibitory effect on lung metastasis of melanoma cells in a dose-dependent manner. A mixture of THFTCA and RGDS peptide or THFTCA alone did not show any inhibitory effect on experimental lung metastasis as compared with FC-243 on a molar basis. RGDS peptide, however, required a higher dose to obtain a sufficient antimetastatic effect. Intermittent IV administration of FC-243 after the inoculation of B16-BL6 cells caused significant inhibition of spontaneous lung metastasis as compared with multiple administration of RGDS or untreated control. The in vitro tumor invasion study showed that FC-243 as well as RGDS+THFTCA on a molar basis resulted in similar inhibition of the invasion of B16-BL6 cells into reconstituted basement membrane Matrigel. Combined treatment with FC-243 and DOX significantly inhibited lung metastasis of melanoma as compared with either treatment alone or the untreated control. Administrations of FC-243 and DOX in combination substantially prolonged the survival time of mice. These results demonstrate that combination therapy of the anti-cell adhesive FC-243 and the anticancer agent DOX, i.e. antiadhesion therapy and chemotherapy, is a new approach that offers enhanced inhibitory effects on tumor metastasis and invasion.

• Authors: H Komazawa, H Fujii, M Kojima, H Mori, M Ono, I Itoh, I Azuma, I Saiki
• Journal: Oncology research (Oncol Res) Vol. 7 Issue 7-8 Pg. 341-51 ( 1995) ISSN: 0965-0407 [Print] United States
• PMID: 8747597 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• FC 243
• Furans
• Oligopeptides
• Doxorubicin
• arginyl-glycyl-aspartyl-serine

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cell Movement (drug effects)
• Dose-Response Relationship, Drug
• Doxorubicin (administration & dosage)
• Female
• Furans (chemical synthesis, pharmacology, therapeutic use)
• Lung Neoplasms (mortality, prevention & control, secondary)
• Melanoma, Experimental (mortality, prevention & control, secondary)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Neoplasm Invasiveness
• Oligopeptides (administration & dosage, chemical synthesis, pharmacology, therapeutic use)
• Skin Neoplasms (pathology)
• Specific Pathogen-Free Organisms
• Tumor Cells, Cultured