title: Antiproliferative and overadditive effects of everolimus and mycophenolate mofetil in pancreas and lung cancer cells in vitro.
abstract: BACKGROUND
  Everolimus inhibits the growth of several tumor cell lines in vitro as well as tumor growth in a rat model. Mycophenolate mofetil (MMF) inhibits growth of a Walker sarcoma in a rat model in vivo. Herein we tested the in vitro antiproliferative capacity of everolimus and MMF on a pancreatic tumor cell line Panc-1 and on a small cell lung cancer cell line ScLc.
  
  
  METHODS
  Cells were cultured under standardized conditions. Everolimus was added in increasing doses from 0.005 to 500 microg/mL; MMF was used from 0.05 to 5000 microg/mL. For co-incubation experiments, we combined everolimus (0.005 microg/mL and 0.05 microg/mL) with five concentrations of MMF; and MMF (0.5 microg/mL and 5 microg/mL) with five concentrations of everolimus. The antiproliferative capacity was assessed by a BrdU incorporation assay.
  
  
  RESULTS
  Everolimus and MMF inhibited BrdU incorporation into Panc-1 and ScLc in a dose-dependent fashion. A 50% inhibition was seen in Panc-1 only at 50 microg/mL everolimus, but in ScLc at 5 microg/mL everolimus. MMF was clearly more potent in Panc-1: 50% inhibition was observed at 5 microg/L. In ScLc, 40% inhibition of BrdU incorporation was seen only at 50 microg/L MMF. In co-incubation, an effective combination for both Panc-1 and ScLc was 5 microg/mL MMF with 0.005 microg/mL everolimus resulting in 50% inhibition of BrdU incorporation (P < .001).
  
  
  CONCLUSIONS
  Everolimus and MMF showed dose-dependent antiproliferative effects in tumor cell lines in vitro both alone and in combination. The combined use of everolimus and MMF showed supra-additive effects at concentrations used for therapeutic immunosuppression in patients.
authors.affiliation: Division of Nephrology, University Hospital Ulm, Ulm, Germany. sylvia.stracke@uni-ulm.de
authors.forename: S
authors.initials: S
authors.lastname: Stracke
authors.forename: L
authors.initials: L
authors.lastname: Ramudo
authors.forename: F
authors.initials: F
authors.lastname: Keller
authors.forename: D
authors.initials: D
authors.lastname: Henne-Bruns
authors.forename: J M
authors.initials: JM
authors.lastname: Mayer
mesh_terms: D000818:Animals; D002279:Carcinoma 256, Walker / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D000068338:Everolimus; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000473:pathology*; D051381:Rats; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D009173:Mycophenolic Acid; D020123:Sirolimus