The Natural Flavonoid Naringenin Inhibits the Cell Growth of Wilms Tumor in Children by Suppressing TLR4/NF-κB Signaling

Author(s):

Hongtao Li*, Peng Chen, Lei Chen and Xinning Wang   Pages 1120 - 1126 ( 7 )

Abstract:

<p>Background: Nuclear Factor-kappa B (NF-&#954;B) is usually activated in Wilms Tumor (WT) cells and plays a critical role in WT development. </P><P> Objective: The study's purpose was to screen for a NF-&#954;B inhibitor from the natural product library and explore its effects on WT development. </P><P> Methods: Luciferase assay was employed to assess the effects of natural chemicals on NF-&#954;B activity. CCK-8 assay was conducted to assess cell growth in response to naringenin. WT xenograft model was established to analyze the effect of naringenin in vivo. Quantitative real-time PCR and Western blot were performed to examine the mRNA and protein levels of relative genes, respectively. </P><P> Results: Naringenin displayed a significant inhibitory effect on NF-&#954;B activation in SK-NEP-1 cells. In SKNEP- 1 and G-401 cells, naringenin inhibited p65 phosphorylation. Moreover, naringenin suppressed TNF-&#945;- induced p65 phosphorylation in WT cells. Naringenin inhibited TLR4 expression at both mRNA and protein levels in WT cells. CCK-8 staining showed that naringenin inhibited cell growth of the two above WT cells in doseand time-dependent manner, whereas Toll-Like Receptor 4 (TLR4) overexpression partially reversed the above phenomena. Besides, naringenin suppressed WT tumor growth in a dose- and time-dependent manner in vivo. Western blot found that naringenin inhibited TLR4 expression and p65 phosphorylation in WT xenograft tumors. </P><P> Conclusion: Naringenin inhibits WT development via suppressing TLR4/NF-&#954;B signaling.</p>

Keywords:

Naringenin, wilms tumor, TLR4, NF-&#954;B, flavonoids, luciferase assay.

Affiliation:

Department of Pediatric Surgery, Cangzhou Central Hospital, No.16 Xinhua West Road, Cangzhou 061000, Hebei, Department of Anesthesiology, Cangzhou Central Hospital, No.16 Xinhua West Road, Cangzhou 061000, Hebei, Department of Pediatric Surgery, Cangzhou Central Hospital, No.16 Xinhua West Road, Cangzhou 061000, Hebei, Department of Pediatric Surgery, Cangzhou Central Hospital, No.16 Xinhua West Road, Cangzhou 061000, Hebei

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