TLR4/MyD88/NF-κB信号通路对LPS诱导的人鼻咽癌5-8F细胞增殖及凋亡的影响

The effect of TLR4/MyD88/NF-κB signaling pathway on proliferation and apoptosis in human nasopharyngeal carcinoma 5-8 Fcells induced by LPS

目的:探讨Toll样受体4(TLR4)/髓样分化因子88(MyD88)通过核转录因子(NF-κB)对体外培养的人鼻咽癌5-8F细胞增殖及凋亡的影响。方法:在内毒素(LPS)诱导下通过PE anti-human特异性抑制TLR4的活性,采用实时荧光定量PCR及Western-blot检测NF-κB及MyD88mRNA和蛋白在人鼻咽癌5-8F细胞的表达,MTT法检测鼻咽癌细胞的增殖抑制率,流式细胞术检测鼻咽癌细胞的凋亡率。结果:通过使用特异性抑制剂MyD88、NF-κB在实验组人鼻咽癌5-8F细胞中的蛋白和mRNA表达水平均低于对照组(P<0.05),NF-κB的下调可抑制人鼻咽癌5-8F细胞的增殖并促进其凋亡。结论:通过抑制TLR4/MyD88信号通路的活性可下调人鼻咽癌5-8F细胞NF-κB基因的表达,抑制细胞增殖并诱导细胞凋亡,其机制与其对NF-κB的调控密切相关。LPS诱导的TLR4/MyD88/NF-κB激活是鼻咽癌发生发展的重要通路,为拓展靶向研究提供了重要依据。

Objective：To evaluate the effects of NF-~B activation on the proliferation and apoptosis through TLR4/MyD88 signaling pathway in human nasopharyngeal carcinoma （NPC） 5-8F cell lines. Method： TLR4 in- duced by LPS is inhibited by PE anti human. Real-Tirne Quantitative PCR and Western blot were employed to evaluate the efficacy of mRNA level and protein expression. The growth inhibition rate of 5-8F by Celecoxib was e-valuated with MTT method. The cell cycle and apoptosis were measured with flow cytometrie method （FCM）. Result： By using the specific inhibitor, the protein and gene expression of NF-nB and MyD88 were both significantly lower than the control group （P〈0.05）. Meanwhile, the down-rugulation of NF-~B could inhibit proliferation of NPC 5-8F cells and promote their apoptosis （P〈0.05）. Conclusion： By inhibiting TLR4 / MyD88 signaling pathway, the expression of NF-κB in NPC 5-8F cells could decrease, then the cell proliferation was inhibited and cell apoptosis was induced. The results showed that TLR4 / MyD88 / NF-κB induced by LPS is an important pathway in the genesis and development of NPC. This study provides evidence for targeting research of NPC.