Research Papers:

NF-κB/RelA-PKM2 mediates inhibition of glycolysis by fenofibrate in glioblastoma cells

Dongfeng Han, Wenjin Wei, Xincheng Chen, Yaxuan Zhang, Yingyi Wang, Junxia Zhang, Xiefeng Wang, Tianfu Yu, Qi Hu, Ning Liu and Yongping You _

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Oncotarget. 2015; 6:26119-26128. https://doi.org/10.18632/oncotarget.4444

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Dongfeng Han1,*, Wenjin Wei1,*, Xincheng Chen1,*, Yaxuan Zhang1,*, Yingyi Wang1, Junxia Zhang1, Xiefeng Wang1, Tianfu Yu1, Qi Hu1, Ning Liu1, Yongping You1

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

*These authors have contributed equally to this work

Correspondence to:

Yongping You, e-mail: [email protected]

Keywords: fenofibrate, PPARα, RelA, PKM2, Warburg effect

Received: February 16, 2015     Accepted: June 19, 2015     Published: June 30, 2015


Aerobic glycolysis (production of lactate from glucose in the presence of oxygen) is a hallmark of cancer. Fenofibrate is a lipid-lowering drug and an agonist of the peroxisome proliferator-activated receptor alpha (PPARα). We found that FF inhibited glycolysis in a PPARα-dependent manner in glioblastoma cells. Fenofibrate inhibited the transcriptional activity of NF-κB/RelA and also disrupted its association with hypoxia inducible factor1 alpha (HIF1α), which is required for the binding of NF-κB/RelA to the PKM promoter and PKM2 expression. High ratios of PKM2/PKM1 promote glycolysis and inhibit oxidative phosphorylation, thus favoring aerobic glycolysis. Fenofibrate decreased the PKM2/PKM1 ratio and caused mitochondrial damage. Given that fenofibrate is a widely used non-toxic drug, we suggest its use in patients with glioblastoma multiforme (GBM).

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