title: Effects of ketamine, s-ketamine, and MK 801 on proliferation, apoptosis, and necrosis in pancreatic cancer cells.
abstract: BACKGROUND
  Adenocarcinoma of the pancreas is one of the most aggressive cancer diseases affecting the human body. The oncogenic potential of this type of cancer is mainly characterized by its extreme growth rate triggered by the activation of signaling cascades. Modern oncological treatment strategies aim at efficiently modulating specific signaling and transcriptional pathways. Recently, anti-tumoral potential has been proven for several substances that are not primarily used in cancer treatment. In some tumor entities, for example, administration of glutamate antagonists inhibits cell proliferation, cell cycle arrest, and finally cell death. To attain endogenic proof of NMDA receptor type expression in the pancreatic cancer cell lines PaTu8988t and Panc-1 and to investigate the impact of ketamine, s-ketamine, and the NMDA receptor antagonist MK 801 on proliferation, apoptosis, and necrosis in pancreatic carcinoma.
  
  
  METHODS
  Cell proliferation was measured by means of the ELISA BrdU assay, and the apoptosis rate was analyzed by annexin V staining. Immunoblotting were also used.
  
  
  RESULTS
  The NMDA receptor type R2a was expressed in both pancreatic carcinoma cell lines. Furthermore, ketamine, s-ketamine, and MK 801 significantly inhibited proliferation and apoptosis.
  
  
  CONCLUSIONS
  In this study, we showed the expression of the NMDA receptor type R2a in pancreatic cancer cells. The NMDA antagonists ketamine, s-ketamine, and MK 801 inhibited cell proliferation and cell death. Further clinical studies are warranted to identify the impact of these agents on the treatment of cancer patients.
authors.affiliation: Department of Anesthesiology, University of Regensburg, Franz Josef Strauss Allee 11, 93053, Regensburg, Germany. Manuela.Malsy@ukr.de.
authors.forename: Manuela
authors.initials: M
authors.lastname: Malsy
authors.affiliation: Department of Anesthesiology, University of Regensburg, Franz Josef Strauss Allee 11, 93053, Regensburg, Germany. Kristina.Gebhardt@ukr.de.
authors.forename: Kristina
authors.initials: K
authors.lastname: Gebhardt
authors.affiliation: Department of Anesthesiology, University of Regensburg, Franz Josef Strauss Allee 11, 93053, Regensburg, Germany. Michael.Gruber@ukr.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Gruber
authors.affiliation: Department of Anesthesiology, University of Regensburg, Franz Josef Strauss Allee 11, 93053, Regensburg, Germany. Christoph.Wiese@ukr.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wiese
authors.affiliation: Department of Anesthesiology, University of Regensburg, Franz Josef Strauss Allee 11, 93053, Regensburg, Germany. Bernhard.Graf@ukr.de.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Graf
authors.affiliation: Department of Anesthesiology, University of Regensburg, Franz Josef Strauss Allee 11, 93053, Regensburg, Germany. Anika.Bundscherer@ukr.de.
authors.forename: Anika
authors.initials: A
authors.lastname: Bundscherer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007649:Ketamine / Q000737:chemistry / Q000494:pharmacology*; D009336:Necrosis / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D013237:Stereoisomerism
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D016291:Dizocilpine Maleate