Low-dose statin treatment increases prostate cancer aggressiveness

Alfredo Caro-Maldonado, Laura Camacho, Amaia Zabala-Letona, Verónica Torrano, Sonia Fernández-Ruiz, Kepa Zamacola-Bascaran, Leire Arreal, Lorea Valcárcel-Jiménez, Natalia Martín-Martín, Juana M. Flores, Ana R. Cortazar, Patricia Zúñiga-García, Amaia Arruabarrena-Aristorena, Fabienne Guillaumond, Diana Cabrera, Juan M. Falcón-Perez, Ana M. Aransay, Antonio Gomez-Muñoz, Mireia Olivan, Juan MoroteArkaitz Carracedo

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Resum

© Caro-Maldonado et al. 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.
Idioma originalAnglès
Pàgines (de-a)1494-1504
RevistaOncotarget
Volum9
Número2
DOIs
Estat de la publicacióPublicada - 1 de gen. 2018

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