J.Jpn. Surg. Soc.. 94(1): 66-70, 1993

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Original article

THE INHIBITORY EFFECT OF NAFAMOSTAT MASILATE（FUT-175）ON LIVER METASTASIS

Basic investigation of inhibitory effect on metastasis of nafamostat mesilate (FUT-175) which is a kind of serine protease inhibitors, was performed. Colon 26 cells were injected to the portal vein of CDF1 mice. FUT-175 at doses of 0.3, 1.0, 3.0, 10.0mg/kg was injected intravenously every 7 day, Mice were sacrificed on day 21, and metastasis of liver surface were measured. The dose dependent reduction of metastasis was observed and reduction of metastasis of mice treated at a dose of 10.0mg/kg was significant. FUT-175 showed no cytotoxicity at doses of 10^-5M or less in vitro, and blood concentration of mice, treated at a dose of 10.0mg/kg, was 2.67×10^-7M. The results showed that inhibitory effect of FUT-175 on metastasis was not caused by direct cytotoxicity. FUT-175 at 2.67×10^-7M in vitro can inhibit only thrombin and plasmin at nearly 50%, and can not inhibit platelet aggregation and collagenase directly. Possible mechanism of inhibition of metastasis is that FUT-175 inhibited both thrombin-mediated platelet aggregation and plasmin-mediated collagenase activation, that arrest and extravasation in cancer cells were inhibited. If protease inhibitor is administered continuously and immediately after surgery, liver metastasis may be prevented.

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