Fenofibrate induces G0/G1 phase arrest by modulating the PPARα/FoxO1/p27kip pathway in human glioblastoma cells
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Fenofibrate, a fibric acid derivative, is known to possess lipid-lowering effects. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcriptional activity has been reported to exhibit anticancer effects, the underlying mechanisms are poorly understood. In this study, we investigated the mechanisms behind the antiproliferative effects of fenofibrate in U87MG cells (human glioma cell line) using the WST-8 Cell Proliferation Assay Kit. Furthermore, we examined genome-wide gene expression profiles and molecular networks using the DAVID online software. Fenofibrate reduced the expression of 405 genes and increased the expression of 2280 genes. DAVID analysis suggested that fenofibrate significantly affected cell cycle progression and pathways involved in cancer, including the mTOR signaling pathway and insulin signaling pathway. Results of flow cytometry analysis indicated that fenofibrate induced cell cycle G0/G1 arrest in U87MG cells. Furthermore, we identified the FoxO1–p27kip signaling axis to be involved in fenofibrate-induced cell cycle arrest. Our findings suggest that in addition to its known lipid-lowering effects, fenofibrate may be used as an antitumor agent in glioma therapy.
KeywordsFenofibrate Peroxisome proliferator-activated receptor alpha (PPARα) Antiproliferation Fork-head box O1 (FoxO1)
This work was supported by grants from the National High Technology Research and Development Program of China (863) (2012AA02A508), Research Special Fund For Public Welfare Industry of Health (201402008), National Natural Science Foundation of China (91229121, 81272792, 81472362,81172389, 81372709, 81302185), Jiangsu Province’s Natural Science Foundation (20131019), Jiangsu Province’s Key Provincial Talents Program (RC2011051), Jiangsu Province’s Key Discipline of Medicine (XK201117), Jiangsu Provincial Special Program of Medical Science (BL2012028), Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
Conflict of interest
- 14.Kojima T, Shimazui T, Horie R, et al. FOXO1 and TCF7L2 genes involved in metastasis and poor prognosis in clear cell renal cell carcinoma. Gene Chromosome Canc. 2010;49:379–89.Google Scholar
- 23.Wilk A, Wyczechowska D, Zapata A, et al. Molecular mechanisms of fenofibrate-induced metabolic catastrophe and glioblastoma cell death. Mol Cell Biol. 2014;57:744.Google Scholar