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


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.


CONCLUSIONS
Tranilast may be a promising new drug for preventing the metastasis of gastric cancer.
Yashiro
Masakazu
M
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. m9312510@med.osaka-cu.ac.jp
Murahashi
Kuniyasu
K
Matsuoka
Tasuku
T
Nakazawa
Kazunori
K
Tanaka
Hiroaki
H
Osaka
Hirohisa
H
Koyama
Tsuyoshi
T
Ohira
Masaichi
M
Chung
Kosei Hirakawa
KH
D002450:Cell Communication / Q000187:drug effects*; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D061965:Matrix Metalloproteinase Inhibitors; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D062367:ortho-Aminobenzoates; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; C012293:tranilast