Prostate cancer patients using cholesterol-lowering statins have 30% lower risk of prostate cancer death compared to non-users. The effect is attributed to the inhibition of the mevalonate pathway in prostate cancer cells. Moreover, statin use causes lipoprotein metabolism changes in the serum. Statin effect on serum or intraprostatic lipidome profiles in prostate cancer patients has not been explored. We studied changes in the serum metabolomic and prostatic tissue lipidome after high-dose 80 mg atorvastatin intervention to expose biological mechanisms causing the observed survival benefit. Our randomized, double-blind, placebo-controlled clinical trial consisted of 103 Finnish men with prostate cancer. We observed clear difference in post-intervention serum lipoprotein lipid profiles between the study arms (median classification error 11.7%). The atorvastatin effect on intraprostatic lipid profile was not as clear (median classification error 44.7%), although slightly differing lipid profiles by treatment arm was observed, which became more pronounced in men who used atorvastatin above the median of 27 days (statin group median classification error 27.2%). Atorvastatin lowers lipids important for adaptation for hypoxic microenvironment in the prostate suggesting that prostate cancer cell survival benefit associated with statin use might be mediated by both, local and systemic, lipidomic/metabolomic profile changes.
Scientific reports. 2020 Jul 21*** epublish ***
Paavo Raittinen, Kati Niemistö, Erika Pennanen, Heimo Syvälä, Seppo Auriola, Jarno Riikonen, Terho Lehtimäki, Pauliina Ilmonen, Teemu Murtola
Department of Mathematics and Systems Analysis, Aalto University School of Science, Helsinki, Finland. ., Tampere University, Tampere, Finland., School of Pharmacy, University of Eastern Finland, Kuopio, Finland., Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland., School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland., Tays Cancer Center, Tampere University Hospital, Tampere, Finland., Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Tampere University, Tampere, Finland., Department of Mathematics and Systems Analysis, Aalto University School of Science, Helsinki, Finland.