Background Pancreatic cancer is a common malignant tumor of the digestive system.It is the fourth major cause of tumor-related death and its morbidity is increasing,and hence it is imperative to develop effective forms of therapy for pancreatic cancer.Peptide tyrosine-tyrosine (PYY) is an important gastrointestinal peptide hormone.According to previous literatures,PYY has been shown to inhibit tumor proliferation in cellular and animal models,but there has been limited research on the detailed mechanism of PYY in pancreatic cancer.This study was to observe the effects of PYY on pancreatic cancer cell and investigate the possible mechanism.Methods The expression of Y1,Y2,and Y5 receptors on pancreatic cancer cell lines were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR).The cytotoxicity of PYY toward the MiaPaCa-2 cell was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; the cell morphology and structure changes were observed under inverted microscope and transmission electron microscope respectively.Apoptosis and cell cycle were evaluated by flow cytometry.The activity of caspase-3 was determined by activity assay kits and West blotting.The expression of survivin,vascular endothelial growth factor (VEGF),and cyclooxygenase-2 (COX-2) were determined by RT-qPCR and West blotting.Results Expression of Y2 receptor is the most abundant PYY receptor on pancreatic cancer cell.PYY inhibited MiaPaCa-2 cell proliferation,blocked it in G0/G1 phase,increased the proportion of apoptosis cells and caspase-3 activity,and reduced the expression of survivin,VEGF,and COX-2.Conclusions PYY weakened the ability of the pancreatic MiaPaCa-2 cell viability through cell cycle blocking and apoptosis inducing.The inhibition effect of PYY may be mediated by the Y2 receptor.The increased caspase-3 activity and reduced expression of survivin,VEGF,and COX-2 may serve as a novel mechanism in PYY inhibition effect on MiaPaCa-2 cell.