Han Dong-feng, Zhang Jun-xia, Wei Wen-jin, Tao Tao, Hu Qi, Wang Ying-yi, Wang Xie-feng, Liu Ning, You Yong-ping
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Tumour Biol. 2015 May;36(5):3823-9. doi: 10.1007/s13277-014-3024-4. Epub 2015 Jan 8.
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.
非诺贝特是一种纤维酸衍生物，已知具有降脂作用。尽管据报道非诺贝特诱导的过氧化物酶体增殖物激活受体α（PPARα）转录活性具有抗癌作用，但其潜在机制尚不清楚。在本研究中，我们使用WST - 8细胞增殖检测试剂盒研究了非诺贝特对U87MG细胞（人胶质瘤细胞系）抗增殖作用的机制。此外，我们使用DAVID在线软件检查了全基因组基因表达谱和分子网络。非诺贝特使405个基因的表达降低，使2280个基因的表达增加。DAVID分析表明，非诺贝特显著影响细胞周期进程以及与癌症相关的通路，包括mTOR信号通路和胰岛素信号通路。流式细胞术分析结果表明，非诺贝特诱导U87MG细胞的细胞周期G0/G1期阻滞。此外，我们确定FoxO1 - p27（kip）信号轴参与非诺贝特诱导的细胞周期阻滞。我们的研究结果表明，除了已知的降脂作用外，非诺贝特可能用作胶质瘤治疗的抗肿瘤药物。
