Effects of lorglumide on growth and invasion of human pancreatic cancer cell line Mia PaCa-2 in vitro through the cholecystokinin-cholecystokinin-1 receptor pathway

摘要: Background: Cholecystokinin (CCK) has been found to be a growth stimulant through its special receptor pathway, especially for gastrointestinal malignancies. Although the CCK-1 shown highly expressed in resected human pancreatic cancer samples, role is less clear. Objective: The aim of this vitro study was investigate expression and function CCK-CCK-1 pathway adenocarcinoma cell line, Mia PaCa-2. Methods: PaCa-2 cells detected by reverse-transcriptase polymerase chain reaction flow cytometry. agonist CCK-8S (the major transmitter form CCK) antagonist lorglumide were cultured respectively with PaCa-2. Three groups created study: group (Mia treated CCK-8S), lorglumide), control alone). Investigators blinded designation. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) cytometry used detect growth, cycle, apoptosis. Apoptosis index rate measured terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. Cell invasion ability observed assay. Expression matrix metalloproteinase-2 (MMP-2) Western blotting. Results: express receptor. Compared (70.2% [1.5%]), associated significant mean (SD) proliferation (85.1% [1.7%]; P = 0.039), ratio S stage cycle increased significantly (50.5% [1.7%] vs 42.2% [1.4%]; 0.021). also (123.8 [1.7] 102.1 [5.8]; 0.005 control). group, inhibited (52.1% [1.8%]; 0.002) (77.6% [1.2%]; 0.003). Lorglumide induced G0/G1 arrest apoptosis (27.1% [3–5%] 3–7% [0.6%]; 0.003 change appeared mediated MMP-2 expression, which upregulated downregulated lorglumide. Conclusion: findings suggest that CCK may exert trophic action on while invasion.