title: Beta-adrenoceptor action on pancreatic cancer cell proliferation and tumor growth in mice.
abstract: OBJECTIVE
  There is growing evidence that some cancer progression is closely associated with beta- adrenoreceptors (β-ARs). However, the underlying mechanisms for β-ARs mediated proliferation of pancreatic cancer cell are poorly understood. In the current study, we evaluated the possible function of β-ARs on the proliferation of human pancreatic ductal adenocarcinomas (PDAC) cell line Panc-1 and explored β-ARsmediated downstream signal pathway.
  
  
  METHODS
  Series of experiments, such as expression of β1- and β2-ARs on pancreatic cancer cell line Panc-1, β-ARsmediated downstream signal pathway activation as well as cell proliferation assay in vitro and in vivo were performed with immunofluorescence, Western blot analysis, BrdU incorporation assays and xenograft tumor growth respectively.
  
  
  RESULTS
  Non-selective β-ARs agonist Isoproterenol (ISO) significantly increased cell proliferation via β-ARs in a dose-dependent manner, with concomitant activation of ERK/MAPK signal pathway in Panc-1 cells. ISO increased expression level of phosphorylated ERK in Panc-1 cells. Furthermore, in vivo study showed that ISO enhanced xenograft tumor growth and this effect was suppressed by non-selective β-ARs antagonist (β-blocker), propranolol (PRO) treatment.
  
  
  CONCLUSIONS
  These findings suggest that the development and progression of PDAC is subject to significant modulation by ISO and PRO and the treatment with PRO may be useful for marker-guided cancer intervention of PDAC. Therefore, PRO may be developed a novel drug for the treatment and intervention of PDAC for its high specificity.
authors.affiliation: Department of Pathology, Jiaxing University College of Medicine, Zhejiang, China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Lin
authors.forename: Kai
authors.initials: K
authors.lastname: Luo
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Lv
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011433:Propranolol; D048049:Extracellular Signal-Regulated MAP Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D007545:Isoproterenol