Transfected cholecystokinin receptors mediate growth inhibitory effects on human pancreatic cancer cell lines

被引:47
作者
Detjen, K [1 ]
Fenrich, MC [1 ]
Logsdon, CD [1 ]
机构
[1] UNIV MICHIGAN,DEPT PHYSIOL,ANN ARBOR,MI 48109
关键词
D O I
10.1053/gast.1997.v112.pm9041258
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 determine the effects of activation of CCK, and CCK, receptors on the growth of human pancreatic cancer cells in vitro. Methods: Two human pancreatic cell lines MiaPaca-2 and Panc-1 were transfected stably with both 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 CCK. CCK treatment caused a sustained pronounced inhibition of anchorage-independent growth. Similarly, CCK treatment inhibited anchorage-dependent growth. Receptor activation caused a concentration and time-dependent reduction in [H-3]thymidine incorporation and nuclear labeling in cells cultured anchored to a plastic substrate. However, these effects on anchorage-dependent growth were transient, suggesting cellular desensitization. Conclusions: These data indicate that both CCK receptor subtypes can mediate growth inhibitory responses in pancreatic cancer cell lines and raise the possibility that CCK exerts a predominant growth inhibitory action on human pancreatic cancer cells.
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页码:952 / 959
页数:8
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