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Fenofibrate induces G0/G1 phase arrest by modulating the PPARα/FoxO1/p27kip pathway in human glioblastoma cells

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Tumor Biology

Abstract

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.

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Acknowledgments

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).

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Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Dong-feng Han, Jun-xia Zhang, Wen-jin Wei, Tao Tao, Qi Hu, Ying-yi Wang, Xie-feng Wang, Ning Liu & Yong-ping You

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  1. Dong-feng Han
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  2. Jun-xia Zhang
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  3. Wen-jin Wei
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  7. Xie-feng Wang
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  9. Yong-ping You
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Corresponding author

Correspondence to Yong-ping You.

Additional information

Dong-feng Han, Jun-xia Zhang, and Wen-jin Wei contributed equally to this work.

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SFigure 1

Positive correlation between FoxO1 and PPARα in GBM samples. (A) FoxO1 showed positive correlation with PPARα in 89 GBM patients downloaded from CGGA. (B) FoxO1 showed positive correlation with PPARα in 169 GBM patients downloaded from TCGA. (TIFF 149 kb)

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Han, Df., Zhang, Jx., Wei, Wj. et al. Fenofibrate induces G0/G1 phase arrest by modulating the PPARα/FoxO1/p27kip pathway in human glioblastoma cells. Tumor Biol. 36, 3823–3829 (2015). https://doi.org/10.1007/s13277-014-3024-4

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  • DOI: https://doi.org/10.1007/s13277-014-3024-4

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