title: Adaptation to statins restricts human tumour growth in Nude mice.
abstract: BACKGROUND
  Statins have long been used as anti-hypercholesterolemia drugs, but numerous lines of evidence suggest that they may also bear anti-tumour potential. We have recently demonstrated that it was possible to isolate cancer cells adapted to growth in the continuous presence of lovastatin. These cells grew more slowly than the statin-sensitive cells of origin. In the present study, we compared the ability of both statin-sensitive and statin-resistant cells to give rise to tumours in Nude mice.
  
  
  METHODS
  HGT-1 human gastric cancer cells and L50 statin-resistant derivatives were injected subcutaneously into Nude mice and tumour growth was recorded. At the end of the experiment, tumours were recovered and marker proteins were analyzed by western blotting, RT-PCR and immunohistochemistry.
  
  
  RESULTS
  L50 tumours grew more slowly, showed a strong decrease in cyclin B1, over-expressed collagen IV, and had reduced laminin 332, VEGF and CD34 levels, which, collectively, may have restricted cell division, cell adhesion and neoangiogenesis.
  
  
  CONCLUSIONS
  Taken together, these results showed that statin-resistant cells developed into smaller tumours than statin-sensitive cells. This may be reflective of the cancer restricting activity of statins in humans, as suggested from several retrospective studies with subjects undergoing statin therapy for several years.
authors: INSERM U613-ECLA and IFR148-ScInBioS, Université Européenne de Bretagne, Université de Bretagne Occidentale, Faculté de médecine, 22 avenue Camille Desmoulins, 29200 Brest, France.
authors: Julie
authors: J
authors: Follet
authors: Lionel
authors: L
authors: Rémy
authors: Vincent
authors: V
authors: Hesry
authors: Brigitte
authors: B
authors: Simon
authors: Danièle
authors: D
authors: Gillet
authors: Pierrick
authors: P
authors: Auvray
authors: Laurent
authors: L
authors: Corcos
authors: Catherine
authors: C
authors: Le Jossic-Corcos
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D056744:Cyclin B1 / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D008148:Lovastatin / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D003094:Collagen; D056744:Cyclin B1; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin; D042461:Vascular Endothelial Growth Factor A; D000097794:Kalinin