Anti-invasive activity of synthetic serine protease inhibitors and its combined effect with a matrix metalloproteinase inhibitor

Takashi Ikeda, Koji Murakami, Yoshihiro Hayakawa, Hideki Fujii, Motohiro Ohkoshi, Ikuo Saiki

Research output: Contribution to journalArticlepeer-review


Tumor invasion into the extracellular matrix (ECM) and basement membrane (BM) is a crucial step of tumor metastasis. In order to investigate the possible therapeutic procedure for the tumor invasion, we investigated the anti-invasive activities of several synthetic serine protease inhibitors. FOY-305, a serine protease inhibitor, showed no cytotoxic activity against human HT-1080 fibrosarcoma cells at concentrations ranging from 0.1 to 100 μg/ml, while its analogs ONO-3403 and FO-349 showed slight cytotoxic activities at the concentration of 100 μg/ml. These compounds inhibited the activity of urokinase-type plasminogen activator (u-PA) which is one of serine proteases and considered to be associated with tumor invasion and metastasis in fibrin zymography. FOY-305 more potently inhibited the invasion of HT-1080 cells into the reconstituted BM Matrigel, as well inhibited u-PA activity, compared with ONO-3403 and FO-349. These results suggest that the anti-invasive activity of these compounds is consistent with their anti-fibrinolytic activities. In addition, the combined treatment of FOY-305 with FC-336 prossessing anti-invasive and anti-MMP properties resulted in marked enhancement of anti-invasive activity. In conclusion, FOY-305 inhibited the invasion of tumor cells through interference with the u-PA activity of tumor cells, and this inhibitory activity was augmented by the combination with a MMP inhibitor.

Original languageEnglish
Pages (from-to)4259-4265
Number of pages7
JournalAnticancer research
Issue number6 A
Publication statusPublished - 1998
Externally publishedYes


  • FOY-305
  • Invasion
  • Serine protease inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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