The effect of bombesin, cholecystokinin, gastrin, and their antagonists on proliferation of pancreatic cancer cell lines.
BACKGROUND
The role of cholecystokinin (CCK) and gastrin in the development and growth of pancreatic cancer cells is controversial. The aim of this study was to evaluate the role of CCK-8S, gastrin-17, bombesin, and their antagonists on cell lines from patients with pancreatic cancer.


METHODS
Cell lines were established from pancreatic cancers operated on at our department. The cells were grown in 10% fetal calf serum (FCS). The effects of CCK-8S, gastrin-17, bombesin, and their antagonists in different concentrations and for different time intervals were studied. The cell number was evaluated with the XTT method.


RESULTS
The cell line LN 36 responded with increased cell number to stimulation by gastrin-17 and decreased cell number to inhibition by the CCK-B receptor antagonist L-365,260. In contrast, LPC 1 responded with increased cell number to CCK-8S and decreased cell number to the CCK-A receptor antagonist devazepide. LPC 2, 6, and 7 were stimulated by CCK-8S, gastrin-17, and their antagonists. LPC 3 showed decreased cell number after inhibition by the antagonists, and LPC 5 and 10 showed increased cell number after stimulation by CCK-8S and gastrin-17. LPC 4 was stimulated by CCK-8S, and LPC 8 was stimulated by all substances except gastrin-17. Intermittent administration of the substances to LN 36 led to a greater effect on the cell number than administration every day, which was not the case with LPC 1 and LPC 3. Bombesin led to an increased growth in LPC 5 but not in LPC 3.


CONCLUSIONS
CCK-8S and gastrin-17 led to an increased cell number in some cell lines. A blockade of the CCK-A and CCK-B receptors by their antagonists led to an increased, an unaffected, or a decreased cell number of the cell lines. The effect of bombesin on different cell lines also varied. This shows a great heterogenicity among pancreatic cancer cells from different patients.
Ohlsson
B
B
Dept. of Surgery, University Hospital, Lund, Sweden.
Fredäng
N
N
Axelson
J
J
D001570:Benzodiazepinones / Q000494:pharmacology; D001839:Bombesin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020109:Devazepide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D010190:Pancreatic Neoplasms / Q000473:pathology*; D010671:Phenylurea Compounds / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D001570:Benzodiazepinones; D005755:Gastrins; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin; D020109:Devazepide; D001839:Bombesin