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

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

Publication date: Jun 07, 2019

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-_705b1 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).

Concepts Keywords
Administrated Alpha
Cancer Fenofibrate
CLI MYD88
Inhibitor Immune system
KB TLR4
Ligand Toll-like receptors
Ligands Fibrates
LPS Chloroarenes
Melanoma Organic compounds
Metastatic Branches of biology
MRNA Medical specialties
Myd88 Anti melanoma
Peroxisome Anti cancer
PPAR Signal transduction melanoma
Receptor Palpable tumors
Signal Transduction Metastatic potential melanoma
Subcutaneously Injected Tumor
Tlr 4
TLR 4
Tlr4
TLR4
TNF
Tumor
Vivo

Semantics

Type Source Name
disease MESH growth
pathway BSID Peroxisome
disease DOID cancer
disease MESH cancer
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
pathway BSID Signal Transduction
gene UNIPROT TLR4
gene UNIPROT PPARA
drug DRUGBANK Fenofibrate
gene UNIPROT NFKB1
gene UNIPROT TNF
gene UNIPROT MYD88
gene UNIPROT CLU
gene UNIPROT IRF6

Original Article

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