title: Peptide tyrosine-tyrosine combined with its receptors exhibits an anti-cancer potential in pancreatic cancer MiaPaCa-2 cell.
abstract: 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 Western blotting. The expression of survivin, vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) were determined by RT-qPCR and Western 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.
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China. Email: diandianliu001@126.com.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China.
authors.forename: Xinsen
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wan
mesh_terms: D015153:Blotting, Western; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D004151:Dipeptides; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A; C042696:tyrosyltyrosine; D051546:Cyclooxygenase 2; D053148:Caspase 3