Objectives: The aim of this study was to evaluate whether the CCK-C receptor, a splice variant of the CCK-B receptor, in human pancreatic cancer cells was associated with accelerated cancer cell growth.
Methods: In vitro, BxPC-3 cells were transfected with the antisense cDNA for the CCK-C receptor and growth of transfected cells was compared with that of wild-type (WT) and empty vector (EV)-transfected cells; expression was confirmed by RT-PCR and immunocytochemistry. In vivo, athymic nude mice bearing human BxPC-3 pancreatic cancers were treated for 28 days with either an antisense oligonucleotide specific to the CCK-C receptor, the same nucleotide sequence arranged in a scrambled fashion (nucleotide control), or vehicle (control).
Results: In culture, BxPC-3 cells transfected with the antisense cDNA for the CCK-C receptor were reduced in cell number 65% compared with WT and EV-transfected cell cultures at 6 days; this difference was statistically significant (P = 0.002). Transfected cells did not respond to exogenous gastrin with growth as did WT cells. Tumors of mice treated with the antisense oligonucleotide for CCK-C were 75% smaller in volume and 83% reduced in weight (P = 0.03) compared with the control tumors.
Conclusion: These studies indicate that the CCK-C receptor is functional and plays a crucial role in growth of human pancreatic cancer.