槲皮素调控NF-κB信号通路对口腔黏膜鳞状细胞癌的化学预防作用

Chemopreventive Effect of Quercetin on Oral Squamous Cell Carcinoma by Regulating NF-κB Signaling Pathway

目的研究槲皮素作为预防药物通过调控NF-κB信号通路对口腔黏膜鳞状细胞癌的化学预防作用机制。方法采用DMBA诱导法建立金黄仓鼠颊囊癌模型随机分为6组阴性对照组、给药组、DMBA模型组、低剂量组(12.5mg/kg)、中剂量组(25mg/kg)、高剂量组(50mg/kg),采用qPCR和Western Blot方法检测NF-κB-p50、NF-κB-p65、IκBα、p-IκBα、IKKβ的表达情况;应用计算机辅助虚拟对接方法对槲皮素与IKKβ激酶分子进行模拟对接。结果 Western blot检测结果表明,中剂量组、高剂量组与模型组相比NF-κB-p50、NF-κB-p65、p-IκBα、IKKβ表达水平降低(P<0.05～0.01),而IκBα表达水平升高(P<0.05～0.01);qPCR检测结果显示,高剂量组与模型组相比NF-κB-p50mRNA、NF-κB-p65mRNA表达水平降低(P<0.05～0.01)。分子模拟对接结果表明,槲皮素通过氢键和π键作用,在同一活性腔中与IKKβ激酶区对接。结论槲皮素可能通过靶向调控NF-κB相关信号通路而发挥对口腔黏膜鳞状细胞癌的化学预防作用。

OBJECTIVE To investigate the chemopreventive effect of quercetin on oral squamous cell carcinoma(OSCC)by regulating NF-κB signaling pathway.METHODS Golden hamster buccal pouch carcinoma model was established by DMBA Induction.The model was divided into 6 groups:blank control group,quercetin administration group,DMBA model group,low dose prevention group,medium dose prevention group,high dose prevention group,qPCR and Western Blot to detect NF-κB.The expressions of NF-κB-p50,NF-κB-p65,IκBα,p-IκBαand IKKβwere detected,and the chemical components of quercetin were docked with IKK beta kinase.Computer-aided virtual docking method was used to simulate the docking of quercetin with IKK beta kinase molecule.RESULTS Western blot analysis showed that the expression levels of NF-κB-p50,NF-κB-p65,p-IκBαand IKKβin medium dose prevention group and high dose prevention group were significantly lower than those in DMBA model group,but the expression levels of IκBαwere significantly higher than those in DMBA model group.qPCR results showed that the expression levels of NF-κB-p50 mRNA and NF-κB-p65 mRNA in high dose prevention group were significantly lower than those in DMBA model group.Molecular simulation docking results showed that quercetin docked with IKK beta kinase region in the same active chamber through hydrogen and PI bonds.CONCLUSION Quercetin may play a chemopreventive role in oral squamous cell carcinoma by targeting the NF-κB signaling pathway.