• Crosstalk between peroxisome proliferator-activated receptor alpha agonist and toll-like receptor 4 in mouse melanoma cancer
  • Nasim Dana,1,* Shaghayegh Haghjooy Javanmard,2 Golnaz Vaseghi,3
    1. Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
    2. Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
    3. Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran


  • Introduction: Background: In the past years despite a wide variety of therapeutic options for melanoma therapy, current survival for patients with metastatic disease is only 6–8 months. There are strong evidences indicating that PPARα activator, fenofibrate, can strongly inhibit melanoma cell progression. However, the mechanism underlying these effects remains to be elucidated. So, we evaluate the effects of this PPARα agonist on Toll-like receptor-4 (TLR-4) signaling in mice melanoma.
  • Methods: Methods: Fifty six C57BL/6 mice were divided to two main groups. One group was injected by LPS (TLR4 agonist) treated B16F10 cells (1 × 106 cells per mouse) subcutaneously and the other group was injected by untreated cells. Tumors were allowed to grow for seven days, and then each group were divided to 4 groups and administered fenofibrate (0, 50, 100, 200 mg/kg/day) for ten days. The tumor volumes were measured at 20 d post injection .We performed quantitative reverse transcriptase-polymerase chain reaction and IHC to access the effect of fenofibrate on Tlr-4 mRNA and protein expression.
  • Results: Results:In the LPS groups, LPS treatment of B16F10 cells before injection caused a significant increase in tumor volume, Tlr-4 mRNA and protein expression compared to the other group that was injected with untreated cells (P < 0.05). Our results indicated that fenofibrate in all concentrations significantly suppressed LPS-stimulated increase of Tlr-4 expression in comparison to LPS group (P < 0.001). We found significantly reduced TLR-4 protein expression in the group that received LPS and fenofibrate50 (mg/kg/day) compared with the LPS group (P < 0.001). Administration of fenofibrate led to a significant reduction in tumor volume in 50 mg/kg/day dose compared to LPS group (P < 0.05).
  • Conclusion: Conclusion: Overall, our findings suggest that fenofibrate may exert its anti-melanoma activity through interaction with TLR4 signaling pathway.
  • Keywords: PPAR alpha , Toll-like receptor-4 , Melanoma