The effect of fenofibrate, a PPARα activator on toll-like receptor-4 signal transduction in melanoma both in vitro and in vivo

  • N. Dana
  • S. Haghjooy Javanmard
  • G. VaseghiEmail author
Research Article



The anti-cancer effect of peroxisome proliferator-activated receptor (PPAR) α ligands on growth and metastatic potential of melanoma cells has been shown previously. However, the mechanism underlying these effects remains to be elucidated. Here, we investigated the effects of fenofibrate (PPAR ligand) on Toll-like receptor-4 (TLR-4) signaling in mice melanoma.


Mice melanoma cells (B16F10) were treated with fenofibrate or LPS or LPS + fenofibrate or pre-treated with CLI-095 (a TLR4 inhibitor), followed by fenofibrate. In in vivo model, C57BL/6 mice were subcutaneously injected with B16F10 cells (with/without LPS pre-treatment), and fenofibrate was administrated after development of palpable tumors. Cell proliferation, the expression level of Tlr4, Myd88, Nf-κb1 genes, TLR-4 protein expression, TNF-α levels, and tumor volume were measured.


Our results indicated that fenofibrate significantly inhibited the Tlr-4, Myd-88, and Nf-kb1 mRNA expression and TNF-α concentration in B16F10 LPS-stimulated cells. In addition, blocking TLR-4 signaling increased the anti-inflammatory potential of fenofibrate. Also fenofibrate can reduce LPS-induced tumor volume, Tlr-4, Myd-88, Nf-kb1 mRNA, and TLR-4 protein expression in tumor tissue and also TNF-α level in tumor tissue lysate.


Our data indicate that fenofibrate may exert its anti-melanoma effects via interaction with TLR4-dependent signaling pathway (TLR-4/MyD-88/ NF-kB).


PPAR alpha Toll-like receptor-4 Melanoma 



This article was derived from a PhD thesis promoted at Isfahan University of Medical Sciences with Grant number of No. 394617. This work was financially supported by Iran National Science Foundation (INSF) [Grant no. 95844116].

Compliance with ethical standards

Conflict of interest

The author(s) declare that they have no conflict of interest.

Ethics approval

The animals were cared for in accordance with the principles and guidelines of the Canadian Council on Animal Care and the use of animals was reviewed and approved by the appropriate animal care review committee at the Ethics Committee of Isfahan University (approval ID: IR. MUI. REC.1394.3.617).

Informed consent

The research did not involve human participants.


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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  1. 1.Applied Physiology Research Center and Department of Physiology, Cardiovascular Research InstituteIsfahan University of Medical SciencesIsfahanIran
  2. 2.Isfahan Cardiovascular Research Center, Cardiovascular Research InstituteIsfahan University of Medical SciencesIsfahanIran

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