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Open Access Highly Accessed Research article

Fenofibrate induces apoptosis of triple-negative breast cancer cells via activation of NF-κB pathway

Ting Li12, Qunling Zhang12, Jian Zhang12, Gong Yang24, Zhimin Shao23, Jianmin Luo23, Minhao Fan12, Chen Ni12, Zhenhua Wu12 and Xichun Hu12*

Author Affiliations

1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, 200032 Shanghai, China

2 Department of Oncology, Shanghai Medical College, Fudan University, 200032 Shanghai, China

3 Department of Breast Surgery, Fudan University Shanghai Cancer Center, 200032 Shanghai, China

4 Department of Cancer Research Laboratory, Fudan University Shanghai Cancer Center, 200032 Shanghai, China

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BMC Cancer 2014, 14:96  doi:10.1186/1471-2407-14-96

Published: 16 February 2014



There are a lot of unmet needs in patients with triple-negative breast cancer (TNBC). Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, has been used for decades to treat hypertriglyceridaemia and mixed dyslipidaemia. Recent studies show that it might have anti-tumor effects, however, the mechanism remains unclear. Here, we assessed the ability of fenofibrate to induce apoptosis of TNBC in vitro and in vivo and explored involved mechanisms.


MTT method was used to evaluate the anti-proliferation effect of fenofibrate, and invert microscope to observe the apoptotic morphological changes. The percentage of apoptotic cells and distribution ratios of cell cycle were determined by flow cytometric analysis. The related protein levels were measured by Western blot method. The changes of genes and pathways were detected by gene expression profiling. The tumor growth in vivo was assessed by MDA-MB-231 xenograft mouse model. Terminal deoxytransferase-catalyzed DNA nick-end labeling (TUNEL) assay was employed to estimate the percentage of apoptotic cells in vivo. In order to evaluate the safety of fenofibrate, blood sampled from rat eyes was detected.


We found that fenofibrate had anti-proliferation effects on breast cancer cell lines, of which the first five most sensitive ones were all TNBC cell lines. Its induction of apoptosis was independent on PPAR-α status with the highest apoptosis percentage of 41.8 ± 8.8%, and it occurred in a time- and dose-dependent manner accompanied by up-regulation of Bad, down-regulation of Bcl-xl, Survivin and activation of caspase-3. Interestingly, activation of NF-κB pathway played an important role in the induction of apoptosis by fenofibtate and the effect could be almost totally blocked by a NF-κB specific inhibitor, pyrrolidine dithiocarbamate (PDTC). In addition, fenofibrate led to cell cycle arrest at G0/G1 phase accompanied by down-regulation of Cyclin D1, Cdk4 and up-regulation of p21, p27/Kip1. In vivo, fenofibrate slowed down tumor growth and induced apoptosis with a good safety profile in the MDA-MB-231 xengograft mouse model.


It is concluded that fenofibrate induces apoptosis of TNBC via activation of NF-κB pathway in a PPAR-α independent way, and may serve as a novel therapeutic drug for TNBC therapy.

Triple-negative breast cancer; Fenofibrate; Anti-proliferation; Apoptosis; NF-κB; Cell cycle arrest