Effect of synthetic protease inhibitor on histologic changes and free radical activity in hamsters with pancreatic cancer.
To investigate the effects of synthetic trypsin inhibitors on pancreatic cancer, camostat (FOY-305) was administered orally to hamsters with experimental pancreatic cancer induced by diisopropanol nitrosamine (DIPN). The effect of free radicals on carcinogenesis was examined by measuring the tissue levels of the scavengers superoxide dismutase (SOD) and glutathione peroxidase (GSX-Px), and pancreatic tissues were examined histologically. Cancers developed in all hamsters that survived 24 weeks in the DIPN group and the FOY group, but 80% of the cancers in the DIPN group were tubular adenocarcinomas, and 91% of those in the FOY group papillary adenocarcinomas. The SOD activity in the DIPN group was significantly lower in the cancerous area and the borderline region than in the non-cancerous region and normal tissue. SOD activity in the cancerous and borderline regions was higher in the FOY groups than in the DIPN group. GSH-Px levels in the borderline and non-cancerous regions were significantly higher in the FOY group than in the DIPN group. These results suggest that the synthetic protease inhibitor slows the progress of pancreatic cancer by its free radical scavenging activity.
Manabe
T
T
First Dept. of Surgery, Faculty of Medicine, Kyoto University, Japan.
Asano
N
N
Yoshimura
T
T
Suwa
H
H
Imamura
T
T
Ohshio
G
G
D000230:Adenocarcinoma / Q000139:chemically induced / Q000188:drug therapy; D000231:Adenocarcinoma, Papillary / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D002273:Carcinogens; D006224:Cricetinae; D004952:Esters; D016166:Free Radical Scavengers; D016670:Gabexate / Q000031:analogs & derivatives*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006146:Guanidines / Q000627:therapeutic use*; D008297:Male; D008647:Mesocricetus; D009602:Nitrosamines; D010179:Pancreas / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000627:therapeutic use*
D002273:Carcinogens; D004952:Esters; D016166:Free Radical Scavengers; D006146:Guanidines; D009602:Nitrosamines; D014361:Trypsin Inhibitors; C034532:camostat; C012457:diisopropanolnitrosamine; D016670:Gabexate; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase