LOXIGLUMIDE (CR1505), A CHOLECYSTOKININ ANTAGONIST, SPECIFICALLY INHIBITS THE GROWTH OF HUMAN PANCREATIC-CANCER LINES XENOGRAFTED INTO NUDE-MICE

Background. Cholecystokinin is thought to be an important factor regul ating the growth of human pancreatic cancers. The study was designed t o evaluate the effects of the cholecystokinin antagonist loxiglumide ( CR1505) on the growth of human pancreatic cancer. Methods. Human gastr ointestinal cancer xenografted tumors (one esophageal, one gastric, tw o colorectal, two biliary tract, and two pancreatic cancers) were tran splanted into nude mice. The mice were given CR1505 at 250 mg/kg daily for 14 days, either subcutaneously or intragastrically, and the tumor volumes before and after treatment were compared. In vitro effects of CR1505 were assessed by measuring the DNA synthesis (H-3-thymidine in corporation). Results. CR1505 inhibited the growth of the two pancreat ic cancer lines but did not inhibit the growth of the other lines. CR1 505 also inhibited in vitro DNA synthesis in the two pancreatic cancer lines at lower concentrations than in the other lines. This pancreati c cancer-specific inhibitory effect of CR1505 was retarded by exogenou sly administered cholecystokinin in one pancreatic cancer line but was augmented in the other line. The effect of CR1505 was inhibited by or al administration of the trypsin-inhibitor camostate (FOY-305) in both pancreatic cancer lines. Conclusions. These results suggest that CR15 05 may specifically inhibit the growth of human pancreatic cancers and may be suitable for clinical study. However, its antiproliferative ef fect may not necessarily be dependent on its cholecystokinin-antagonis m but may be mediated through the proteolytic enzymes found in the lys osomes of the pancreatic cancer cells.