Intraperitoneal infusion of recombinant plasminogen activator inhibitor type 2 induced apoptosis in implanted human colon cancer and inhibited its growth and liver metastasis.

Antitumor effects of plasminogen activator (PA) inhibitors (PAls) were analyzed in a mouse model of human colon cancer xenografts. Either recombinant PA inhibitor-1 (rPAI-1) or inhibitor-2 (rPAI-2) was injected intraperitoneally to nude mice bearing human colon cancer xenografts for 6 weeks. Primary tumors in rPAI-2-treated group were smaller (0.45 +/- 0.13 g, n = 16) than in the other two groups (control: 0.73 +/- 0.24 g, n = 15; rPAI-1: 0.62 +/- 0.29 g, n = 19). Primary tumors in the rPAI-2-treated group exhibited less mature ductal structures and were significantly smaller. The apoptotic index was higher in the rPAI-2-treated group (4.64 +/- 2.12%) than in the other groups (control: 1.94 +/- 0.82%; rPAI-1: 2.08 +/- 1.07%). Liver metastasis was less frequent in the rPAI-1 (5/19) and rPAI-2-treated groups (1/16) than in the control group (14/15). PAI-2 more effectively suppressed tumor metastasis and progression, probably by inducing apoptosis; some different unknown mechanism may cause the difference in both antitumor effect and the histological findings. This may indicate the therapeutic potential of these PAls in malignant patients.