CIC bioGUNE
Published October 31, 2017 | Version v1
Journal article Open

Low-dose statin treatment increases prostate cancer aggressiveness

Authors/Creators

  • 1. CIC bioGUNE, Bizkaia Technology Park, Derio, Spain
  • 2. CIC bioGUNE, Bizkaia Technology Park, Derio, Spain; Biochemistry and Molecular Biology Department, University of the Basque Country, Bilbao, Spain
  • 3. CIC bioGUNE, Bizkaia Technology Park, Derio, Spain; CIBERONC, Madrid, Spain
  • 4. Department of Animal Medicine and Surgery, School of Veterinary Medicine, Complutense University of Madrid, Madrid, Spain
  • 5. Centre de Recherche en Cancérologie de Marseille, U1068, Institut National de la Santé et de la Recherche Médicale, Paris, France; Institut Paoli-Calmettes, Marseille, France; UMR 7258, Centre National de la Recherche Scientifique, Paris, France;Université Aix-Marseille, Marseille, France
  • 6. CIC bioGUNE, Bizkaia Technology Park, Derio, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain; IKERBASQUE, Basque foundation for science, Bilbao, Spain
  • 7. CIC bioGUNE, Bizkaia Technology Park, Derio, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
  • 8. Biochemistry and Molecular Biology Department, University of the Basque Country, Bilbao, Spain
  • 9. Department of Urology and Research Group in Urology, Vall d´Hebron Hospital, Vall d´Hebron Research Institute, and Universitat Autònoma de Barcelona, Barcelona, Spain
  • 10. CIC bioGUNE, Bizkaia Technology Park, Derio, Spain; Biochemistry and Molecular Biology Department, University of the Basque Country, Bilbao, Spain; CIBERONC, Madrid, Spain; IKERBASQUE, Basque foundation for science, Bilbao, Spain

Description

Prostate cancer is diagnosed late in life, when co-morbidities are frequent. Among them, hypertension, hypercholesterolemia, diabetes or metabolic syndrome exhibit an elevated incidence. In turn, prostate cancer patients frequently undergo chronic pharmacological treatments that could alter disease initiation, progression and therapy response. Here we show that treatment with anti-cholesterolemic drugs, statins, at doses achieved in patients, enhance the pro-tumorigenic activity of obesogenic diets. In addition, the use of a mouse model of prostate cancer and human prostate cancer xenografts revealed that in vivo simvastatin administration alone increases prostate cancer aggressiveness. In vitro cell line systems supported the notion that this phenomenon occurs, at least in part, through the direct action on cancer cells of low doses of statins, in range of what is observed in human plasma. In sum, our results reveal a prostate cancer experimental system where statins exhibit an undesirable effect, and warrant further research to address the relevance and implications of this observation in human prostate cancer.

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