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.
Departments of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan. dsuwa@apost.plala.or.jp
Daihachiro
D
Suwa
Hiroyuki
H
Konno
Tatsuo
T
Tanaka
Tetsumei
T
Urano
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004341:Drug Evaluation; D006801:Humans; D007263:Infusions, Parenteral; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017396:Plasminogen Activator Inhibitor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D017396:Plasminogen Activator Inhibitor 2; D011994:Recombinant Proteins