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Loxiglumide (CR1505), a cholecystokinin antagonist, specifically inhibits the growth of human pancreatic cancer lines xenografted into nude mice.
- Source :
-
Cancer [Cancer] 1993 Dec 15; Vol. 72 (12), pp. 3599-606. - Publication Year :
- 1993
-
Abstract
- Background: Cholecystokinin is thought to be an important factor regulating the growth of human pancreatic cancers. The study was designed to evaluate the effects of the cholecystokinin antagonist loxiglumide (CR1505) on the growth of human pancreatic cancer.<br />Methods: Human gastrointestinal cancer xenografted tumors (one esophageal, one gastric, two colorectal, two biliary tract, and two pancreatic cancers) were transplanted 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 (3H-thymidine incorporation).<br />Results: CR1505 inhibited the growth of the two pancreatic cancer lines but did not inhibit the growth of the other lines. CR1505 also inhibited in vitro DNA synthesis in the two pancreatic cancer lines at lower concentrations than in the other lines. This pancreatic cancer-specific inhibitory effect of CR1505 was retarded by exogenously administered cholecystokinin in one pancreatic cancer line but was augmented in the other line. The effect of CR1505 was inhibited by oral administration of the trypsin-inhibitor camostate (FOY-305) in both pancreatic cancer lines.<br />Conclusions: These results suggest that CR1505 may specifically inhibit the growth of human pancreatic cancers and may be suitable for clinical study. However, its antiproliferative effect may not necessarily be dependent on its cholecystokinin-antagonism but may be mediated through the proteolytic enzymes found in the lysosomes of the pancreatic cancer cells.
- Subjects :
- Animals
Cell Division drug effects
Chloroquine pharmacology
DNA biosynthesis
Esters
Guanidines pharmacology
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Transplantation
Organ Culture Techniques
Proglumide pharmacology
Proglumide therapeutic use
Sincalide pharmacology
Transplantation, Heterologous
Cholecystokinin antagonists & inhibitors
Gabexate analogs & derivatives
Pancreatic Neoplasms drug therapy
Proglumide analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0008-543X
- Volume :
- 72
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 8252474
- Full Text :
- https://doi.org/10.1002/1097-0142(19931215)72:12<3599::aid-cncr2820721209>3.0.co;2-8