Tranilast (N-3,4-dimethoxycinamoyl anthranilic acid): a novel inhibitor of invasion-stimulating interaction between gastric cancer cells and orthotopic fibroblasts.

ABSTRACT

BACKGROUND: Fibroblasts produce various cytokines that affect the invasion ability of cancer cells. We have previously reported that gastric fibroblasts play an important role in the metastatic process of gastric cancer. Tranilast is a clinical drug for inhibition of fibroblast growth. To develop a drug for cancer invasion, the effect of Tranilast on the invasion-stimulating interaction was examined. MATERIALS AND METHODS: The human gastric carcinoma cell line, OCUM-2D, and the gastric fibroblast cell line, NF-10, were used. The effect of Tranilast on the invasion ability of OCUM-2D cells with NF-10 cells was examined by invasion assay. RESULTS: The invasion ability of OCUM-2D cells was significantly increased by co-culturing with NF-10 cells (p < 0.01). Tranilast, at concentrations of more than 0.01 mM, significantly suppressed the invasion ability of OCUM-2D cells co-cultured with NF-10 cells. Tranilast decreased matrix metalloproteinase-2 (MMP-2) and transforming growth factor-beta 1 (TGF-beta 1) production from fibroblasts. TGF-beta 1 enhanced the MMP-2 production from fibroblasts. The invasion ability of gastric cancer cells was increased by MMP-2 and TGF-beta 1 from fibroblasts and this effect was inhibited by Tranilast, which decreased the MMP-2 and TGF-beta 1 production from fibroblasts. CONCLUSION: Tranilast may be a promising new drug for preventing the metastasis of gastric cancer.