title: Dexamethasone reduces tumor recurrence and metastasis after pancreatic tumor resection in SCID mice.
abstract: BACKGROUND
  Glucocorticoids are among the most potent anti-inflammatory agents that act by inhibiting the synthesis of almost all known cytokines and influencing multiple transduction pathways. Inflammation accompanies most solid cancers including pancreatic ductal adenocarcinoma (PDAC), one of the most fatal cancers with surgery being the only potential curative therapeutic. In the present work we investigated the influence of glucocorticoids on PDAC cells in vitro as well as in vivo in a pancreatic carcinoma resection mouse model.
  
  
  METHODS
  The influence of dexamethasone (DEX), a synthetic glucocorticoid, on proliferation and IL8 secretion in pancreatic cells (BxPC3, Colo357, PancTuI) was analyzed by cell counting and ELISA. NFkappaB-activity of PancTuI cells treated with DEX was determined by electrophoretic mobility shift assay (EMSA). Furthermore, effects of DEX on the invasiveness were studied by a fibroblast-based invasion assay. In the mouse resection model subtotal pancreatectomy was performed after orthotopic inoculation of human PDAC cells. DEX was administered after resection as an adjuvant treatment regime and 4 weeks later, local recurrent tumor sizes as well as number of liver and spleen metastases were analyzed.
  
  
  RESULTS
  In vitro, DEX did not have an anti-proliferative effect on PDAC cells, but strongly reduced the invasiveness well as the activation of NFkappaB. The secretion of IL-8 into the supernatant of the tumor cells correlated inversely with the reduced activation of NFkappaB. In vivo, we observed a significant reduction of the local recurrent tumor volume and the number of liver and spleen metastases.
  
  
  CONCLUSIONS
  DEX has a profound influence on the malignant phenotype of PDAC tumor cells in vitro in terms of inhibition of invasiveness and pro-inflammatory signaling. This was approved in vivo by reduced metastasizing capacity and reduced size of local tumor recurrence. Therefore, DEX-treatment appears to be an interesting therapeutical option in an adjuvant setting after pancreatic cancer resection.
authors.affiliation: Division of Molecular Oncology, Department of General Surgery and Thoracic Surgery, University Hospital of Schleswig-Holstein, Kiel, Germany.
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Egberts
authors.forename: Bodo
authors.initials: B
authors.lastname: Schniewind
authors.forename: Miriam
authors.initials: M
authors.lastname: Pätzold
authors.forename: Bastian
authors.initials: B
authors.lastname: Kettler
authors.forename: Jürgen
authors.initials: J
authors.lastname: Tepel
authors.forename: Holger
authors.initials: H
authors.lastname: Kalthoff
authors.forename: Anna
authors.initials: A
authors.lastname: Trauzold
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D012008:Recurrence; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003907:Dexamethasone