Tumor growth inhibition mediated by trypsin inhibitor or urokinase inhibitors

Abstract

When testing in vitro, we often observed that erythrocytes taken from Ehrlich ascites tumor bearing mice displayed enhanced agglutinability by the lectin Concanavalin A, suggesting that protease activity operates in vivo. In several studies, we were able to inhibit Ehrlich ascites tumor growth by the repeated administration of soya bean trypsin inhibitor. Studies of dosages and schedules of treatment showed that for 20,000 initially grafted cells, treatment resulted in 0–70% of long-term survivors and induced a significant increase in mean survival time of treated mice over control mice. For 200,000 grafted tumor cells, 0–40% of long-term survivors were recorded. In a comparative study, we found that different inhibitors of urokinase displayed a similar chemotherapeutic effect against 200,000 inoculated cells. Our results corroborate the idea that a plasminogen activator monitored chain of fibrinolytic and proteolytic activity controls tumor growth and metastasis enzymatically.