title: Glaucarubinone Combined with Gemcitabine Improves Pancreatic Cancer Survival in an Immunocompetent Orthotopic Murine Model.
abstract: BACKGROUND
  Pancreatic cancer continues to have a poor survival rate with an urgent need for improved treatments. Glaucarubinone, a natural product first isolated from the seeds of the tree Simarouba glauca, has recently been recognized as having anti-cancer properties that may be particularly applicable to pancreatic cancer.
  
  
  METHODS
  The effect of glaucarubinone on the growth and migration of murine pancreatic cancer cells was assessed by3H-thymidine incorporation assay. The survival impact of glaucarubinone alone and in combination with gemcitabine chemotherapy was assessed using an immunocompetent orthotopic murine model of pancreatic cancer.
  
  
  RESULTS
  Glaucarubinone inhibited the growth of the murine pancreatic cancer cell lines LM-P and PAN02. Treatment with either glaucarubinone or gemcitabine reduced proliferation in vitro and the combination was synergistic. The combination treatment improved survival two-fold compared to gemcitabine treatment alone (p = 0.046) in PAN02 cells.
  
  
  CONCLUSIONS
  The synergistic inhibition by glaucarubinone and gemcitabine observed in vitro and the improved survival in vivo suggest that glaucarubinone may be a useful adjunct to current chemotherapy regimens.
authors.affiliation: a Department of Surgery , University of Melbourne, Austin Health , Melbourne , Victoria , Australia.
authors.forename: Dannel
authors.initials: D
authors.lastname: Yeo
authors.affiliation: a Department of Surgery , University of Melbourne, Austin Health , Melbourne , Victoria , Australia.
authors.forename: Nhi
authors.initials: N
authors.lastname: Huynh
authors.affiliation: b Molecular Targets Laboratory, National Cancer Institute , Frederick , MD.
authors.forename: John A
authors.initials: JA
authors.lastname: Beutler
authors.affiliation: a Department of Surgery , University of Melbourne, Austin Health , Melbourne , Victoria , Australia.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Baldwin
authors.affiliation: a Department of Surgery , University of Melbourne, Austin Health , Melbourne , Victoria , Australia.
authors.forename: Hong
authors.initials: H
authors.lastname: He
authors.affiliation: a Department of Surgery , University of Melbourne, Austin Health , Melbourne , Victoria , Australia.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Nikfarjam
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000401:mortality; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D005900:Glaucarubin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000401:mortality; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; C015235:glaucarubinone; D005900:Glaucarubin; D000093542:Gemcitabine
keywords: gemcitabine; glaucarubinone; pancreatic cancer; survival