Background: Nuclear factor-kappa B (NF-κB) is usually activated in Wilms Tumor (WT) cells and
plays a critical role in WT development.
Objective: The study's purpose was to screen for a NF-κB inhibitor from the natural product library and explore
its effects on WT development.
Methods: Luciferase assay was employed to assess the effects of natural chemicals on NF-κB 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.
Results: Naringenin displayed a significant inhibitory effect on NF-κB activation in SK-NEP-1 cells. In SKNEP-
1 and G-401 cells, naringenin inhibited p65 phosphorylation. Moreover, naringenin suppressed TNF-α-
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.
Conclusion: Naringenin inhibits WT development via suppressing TLR4/NF-κB signaling.