title: Simvastatin impairs murine melanoma growth.
abstract: BACKGROUND
  Statins induces cell cycle arrest, apoptosis, reduction of angiogenic factors, inhibition of the endothelial growth factor, impairing tissue adhesion and attenuation of the resistance mechanisms. The aim of this study was evaluate the anti-tumoral activity of simvastatin in a B16F10 melanoma-mouse model.
  
  
  METHODS
  Melanoma cells were treated with different concentrations of simvastatin and assessed by viability methods. Melanoma cells (5 × 10(4)) were implanted in two month old C57Bl6/J mice. Around 7 days after cells injection, the oral treatments were started with simvastatin (5 mg/kg/day, p.o.). Tumor size, hematological and biochemical analyses were evaluated.
  
  
  RESULTS
  Simvastatin at a concentration of 0.8 μM, 1.2 μM and 1.6 μM had toxic effect. Concentration of 1.6 μM induced a massive death in the first 24 h of incubation. Simvastatin at 0.8 μM induces early cell cycle arrest in G0/G1, followed by increase of hypodiploidy. Tumor size were evaluated and the difference of treated group and control, after ten days, demonstrates that simvastatin inhibited the tumor expansion in 68%.
  
  
  CONCLUSIONS
  Simvastatin at 1.6 μM, presented cytototoxicity after 72 h of treatment, with an intense death. In vivo, simvastatin being potentially useful as an antiproliferative drug, with an impairment of growth after ten days.
authors.affiliation: State University of Ponta Grossa, Biological and Health Science Multidisciplinary Laboratory, Ponta Grossa, Brazil. gmfavero@uepg.br
authors.forename: Giovani M
authors.initials: GM
authors.lastname: Favero
authors.forename: Michel
authors.initials: M
authors.lastname: F Otuki
authors.forename: Karen A
authors.initials: KA
authors.lastname: Oliveira
authors.forename: Milton S
authors.initials: MS
authors.lastname: Bohatch
authors.forename: Primavera
authors.initials: P
authors.lastname: Borelli
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Barros
authors.forename: Durvanei A
authors.initials: DA
authors.lastname: Maria
authors.forename: Daniel
authors.initials: D
authors.lastname: Fernandes
authors.forename: Sergio P
authors.initials: SP
authors.lastname: Bydlowski
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D008099:Liver / Q000187:drug effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019821:Simvastatin / Q000627:therapeutic use*; D013154:Spleen / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D019821:Simvastatin