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

Hiroyuki Komazawa, Hideki Fujii, Masayoshi Kojima, Hideto Mori, Mitsunori Ono, Isamu Itoh, Ichiro Azuma, Ikuo Saiki

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)341-351
Number of pages11
JournalOncology research
Volume7
Issue number7-8
Publication statusPublished - 1995
Externally publishedYes

Keywords

  • anticancer drug
  • fibronectin
  • invasiveness
  • metastasis
  • synthetic Arg-Gly-Asp-Ser analogue

ASJC Scopus subject areas

  • General Medicine

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