Stimulating effect of normal-dosing of fibrates on cell proliferation: word of warning

Lipids in Health and Disease

Research

Jana Steigerova¹  Katerina Cizkova²  Jiri Ehrmann³  Jan Gursky⁴ 

[1] Department of Clinical and Molecular Pathology & Laboratory of Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, 775 15, Olomouc, Czech Republic;Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 775 15, Olomouc, Czech Republic;Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 775 15, Olomouc, Czech Republic;Department of Clinical and Molecular Pathology & Laboratory of Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, 775 15, Olomouc, Czech Republic;Institute of Molecular and Translation Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 5, 775 15, Olomouc, Czech Republic;

关键词: Peroxisome proliferator-activated receptor α;    Hypolipidemic drugs;    Proliferation;    CYP Epoxygenases;    Epoxyeicosatrienoic acids;    Cancer;   

DOI  :  10.1186/s12944-016-0335-z

 received in 2016-04-14, accepted in 2016-09-14,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundFibrates are widely used hypolipidemic drugs, which serve as ligand of peroxisome proliferator-activated receptor α (PPARα). Recently, they have also been considered as potential anticancer agents. We studied effect of fibrates treatment on cell proliferation, expression of CYP2J2 and concomitant changes in expression of cell cycle regulatory proteins in three different human cell lines: HEK293, HepG2, and HT-29.MethodsWe used WST-1 viability test, western blot and immunocytochemistry for detection of proteins of interests and analysis of cell cycle.ResultsOur results showed that at lower concentrations of all tested fibrates, viability of all tested cell lines is increased, whereas at higher concentrations, repression is apparent. Unfortunately, the viability of tested cells is predominantly increased in a range of concentration which is reached in patient plasma. This phenomenon is accompanyed by elevation of CYP2J2, increased number of cyclin E-positive cells and decreased number of Cdc25A-positive cells in all tested cell lines, and elevated cyclin A expression in HepG2 and HT-29. These changes are concentration-dependent. We suppose that increased level of CYP2J2 could explain enhanced cell proliferation in lower concentration of fibrates.ConclusionBased on our results, we suggested there is no anti-cancer effect of fibrates in tested carcinoma cell lines.

【 授权许可】

CC BY   
© The Author(s). 2016