柚皮素通过抑制 TLR4/NF-κB 信号通路抑制儿童肾母细胞瘤的细胞生长。
The Natural Flavonoid Naringenin Inhibits the Cell Growth of Wilms Tumor in Children by Suppressing TLR4/NF-κB Signaling.
机构信息
Department of Pediatric Surgery, Cangzhou Central Hospital, No.16 Xinhua West Road, Cangzhou 061000, Hebei, China.
Department of Anesthesiology, Cangzhou Central Hospital, No.16 Xinhua West Road, Cangzhou 061000, Hebei, China.
出版信息
Anticancer Agents Med Chem. 2021;21(9):1120-1126. doi: 10.2174/1871520620999200818155814.
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.
背景
核因子-κB（NF-κB）通常在肾母细胞瘤（WT）细胞中被激活，并在 WT 发育中发挥关键作用。
目的
本研究旨在从天然产物文库中筛选 NF-κB 抑制剂，并探讨其对 WT 发育的影响。
方法
采用荧光素酶 assay 评估天然化学物质对 NF-κB 活性的影响。CCK-8 assay 检测柚皮素对细胞生长的影响。建立 WT 异种移植模型，分析柚皮素在体内的作用。定量实时 PCR 和 Western blot 分别检测相对基因的 mRNA 和蛋白水平。
结果
柚皮素对 SK-NEP-1 细胞中的 NF-κB 激活具有显著的抑制作用。在 SKNEP-1 和 G-401 细胞中，柚皮素抑制 p65 磷酸化。此外，柚皮素抑制 WT 细胞中 TNF-α诱导的 p65 磷酸化。柚皮素在 WT 细胞中抑制 TLR4 的表达，无论是在 mRNA 水平还是在蛋白水平。CCK-8 染色显示，柚皮素以剂量和时间依赖的方式抑制两种上述 WT 细胞的细胞生长，而 Toll 样受体 4（TLR4）过表达部分逆转了上述现象。此外，柚皮素在体内以剂量和时间依赖的方式抑制 WT 肿瘤的生长。Western blot 发现，柚皮素抑制 WT 异种移植肿瘤中 TLR4 表达和 p65 磷酸化。
结论
柚皮素通过抑制 TLR4/NF-κB 信号通路抑制 WT 发育。
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