title: The association of statins and taxanes: an efficient combination trigger of cancer cell apoptosis.
abstract: BACKGROUND
  Cancer cell killing might be achieved by the combined use of available drugs. Statins are major anti-hypercholesterolemia drugs, which also trigger apoptosis of many cancer cell types, while docetaxel is a potent microtubule-stabilising agent.
  
  
  METHODS
  Here, we looked at the combined effects of lovastatin and docetaxel in cancer cells.
  
  
  RESULTS
  Whole transcriptome microarrays in HGT-1 gastric cancer cells demonstrated that lovastatin strongly suppressed expression of genes involved in cell division, while docetaxel had very little transcriptional effects. Both drugs triggered apoptosis, and their combination was more than additive. A marked rise in the cell-cycle inhibitor p21, together with reduction of aurora kinases A and B, cyclins B1 and D1 proteins was induced by lovastatin alone or in combination with docetaxel. The drug treatments induced the proteolytic cleavage of procaspase-3, a drop of the anti-apoptotic Mcl-1 protein, Poly-ADP-Ribose Polymerase and Bax. Strikingly, docetaxel-resistant HGT-1 cell derivatives overexpressing the MDR-1 gene were much more sensitive to lovastatin than docetaxel-sensitive cells.
  
  
  CONCLUSIONS
  These results suggest that the association of lovastatin and docetaxel, or lovastatin alone, shows promise as plausible anticancer strategies, either as a direct therapeutic approach or following acquired P-glycoprotein-dependent resistance.
authors.affiliation: Inserm U613-ECLA Team, Faculté de Médecine, Université Européenne de Bretagne, Université de Bretagne Occidentale, IFR 148-ScInBioS, 22 Avenue Camille Desmoulins, 29200 Brest, France.
authors.forename: J
authors.initials: J
authors.lastname: Follet
authors.forename: L
authors.initials: L
authors.lastname: Corcos
authors.forename: G
authors.initials: G
authors.lastname: Baffet
authors.forename: F
authors.initials: F
authors.lastname: Ezan
authors.forename: F
authors.initials: F
authors.lastname: Morel
authors.forename: B
authors.initials: B
authors.lastname: Simon
authors.forename: C
authors.initials: C
authors.lastname: Le Jossic-Corcos
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004351:Drug Resistance / Q000187:drug effects / Q000276:immunology; D004357:Drug Synergism; D006801:Humans; D008148:Lovastatin / Q000008:administration & dosage* / Q000494:pharmacology; D046228:Microarray Analysis; D059748:Proteolysis; D043823:Taxoids / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D008148:Lovastatin