title: Fenofibrate induces G0/G1 phase arrest by modulating the PPARα/FoxO1/p27 kip pathway in human glioblastoma cells.
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-p27(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.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Dong-feng
authors.initials: DF
authors.lastname: Han
authors.forename: Jun-xia
authors.initials: JX
authors.lastname: Zhang
authors.forename: Wen-jin
authors.initials: WJ
authors.lastname: Wei
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.forename: Qi
authors.initials: Q
authors.lastname: Hu
authors.forename: Ying-yi
authors.initials: YY
authors.lastname: Wang
authors.forename: Xie-feng
authors.initials: XF
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Yong-ping
authors.initials: YP
authors.lastname: You
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D011345:Fenofibrate / Q000008:administration & dosage*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015894:Genome, Human; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis; D047493:PPAR alpha / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins; D047493:PPAR alpha; D050760:Cyclin-Dependent Kinase Inhibitor p27; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D011345:Fenofibrate