TRANSFECTED CHOLECYSTOKININ RECEPTORS MEDIATE GROWTH-INHIBITORY EFFECTS ON HUMAN PANCREATIC-CANCER CELL-LINES

Background & Aims: Cholecystokinin (CCK) acting via CCK, receptors and gastrin acting via CCK, receptors exert trophic effects on a variety of nontransformed tissues. However, their role as hormonal regulators of pancreatic cancer is controversial. The aim of this study was to de termine the effects of activation of CCK, and CCK, receptors on the gr owth of human pancreatic cancer cells in vitro. Methods: Two human pan creatic cell lines MiaPaca-2 and Panc-1 were transfected stably with b oth CCK receptor subtypes. Effects of CCK on various growth parameters including DNA synthesis, nuclear labeling, and colony formation were evaluated. Results: Cells expressing either receptor subtype, but not untransfected cells, bound ligand and mobilized Ca2+ in response to CC K. CCK treatment caused a sustained pronounced inhibition of anchorage -independent growth. Similarly, CCK treatment inhibited anchorage-depe ndent growth. Receptor activation caused a concentration and time-depe ndent reduction in [H-3]thymidine incorporation and nuclear labeling i n cells cultured anchored to a plastic substrate. However, these effec ts on anchorage-dependent growth were transient, suggesting cellular d esensitization. Conclusions: These data indicate that both CCK recepto r subtypes can mediate growth inhibitory responses in pancreatic cance r cell lines and raise the possibility that CCK exerts a predominant g rowth inhibitory action on human pancreatic cancer cells.