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Tumor Biology

, Volume 36, Issue 5, pp 3823–3829 | Cite as

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

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

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.

Keywords

Fenofibrate Peroxisome proliferator-activated receptor alpha (PPARα) Antiproliferation Fork-head box O1 (FoxO1) 

Notes

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).

Conflict of interest

None

Supplementary material

13277_2014_3024_MOESM1_ESM.tif (149 kb)
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)
13277_2014_3024_Fig5_ESM.gif (14 kb)

High resulotion image (GIF 13 kb)

13277_2014_3024_MOESM2_ESM.xlsx (183 kb)
ESM 2 (XLSX 183 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Dong-feng Han
    • 1
  • Jun-xia Zhang
    • 1
  • Wen-jin Wei
    • 1
  • Tao Tao
    • 1
  • Qi Hu
    • 1
  • Ying-yi Wang
    • 1
  • Xie-feng Wang
    • 1
  • Ning Liu
    • 1
  • Yong-ping You
    • 1
  1. 1.Department of NeurosurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina

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