Fenofibrate induces G^sub 0^/G^sub 1^ phase arrest by modulating the PPAR[alpha]/FoxO1/p27^sup kip^ pathway in human glioblastoma cells

• Published in: Tumor biology 2015-05, Vol.36 (5), p.3823
• Main Authors: Han, Dong-feng, Zhang, Jun-xia, Wei, Wen-jin, Tao, Tao, Hu, Qi, Wang, Ying-yi, Wang, Xie-feng, Liu, Ning, You, Yong-ping
• Format: Article
• Language: English
• Subjects: Brain cancer; Cell growth; Drug therapy; Signal transduction
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-014-3024-4

Fenofibrate, a fibric acid derivative, is known to possess lipid-lowering effects. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPAR[alpha]) 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 G^sub 0^/G^sub 1^ arrest in U87MG cells. Furthermore, we identified the FoxO1-p27^sup kip^ 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.