Notch信号阻断剂抑制鼻咽癌细胞增殖的作用及机制

doi:10.3971/j.issn.1000-8578.2011.12.001

Notch信号阻断剂抑制鼻咽癌细胞增殖的作用及机制

Expression and Role of Notch Signaling Pathway in Nasopharyngeal Carcinoma Cells

摘要

摘要: 目的探讨Notch信号阻断剂抑制鼻咽癌细胞增殖的作用及其机制。方法应用Notch信号特异性抑制剂GSI抑制Notch信号的表达，MTT法检测癌细胞的生长增殖变化；流式细胞及Hoechst 33258染色检测癌细胞凋亡；应用Western blot检测Notch信号受抑制后AKT、MEK信号通路的变化。结果应用Notch抑制剂GSI作用后，癌细胞Notch1、2、4表达明显下降，而Notch3无明显变化。GSI作用后癌细胞增殖明显受到抑制，凋亡增加；该作用有浓度及时间双重依赖性（P<0.05）。Notch信号阻断后磷酸化AKT、GSK3β和ERK1/2显著下降，而总AKT、总GSK3β及总ERK1/2无明显变化。结论阻断鼻咽癌细胞Notch信号可以显著抑制鼻咽癌细胞增殖及诱导癌细胞凋亡。该作用可能与下调AKT及MEK信号通路有关。

Abstract: Objective To investigate the role of the Notch signaling in NPC cells. MethodsThe expression of Notch receptors was detected in 5-8F cells and CNE-1 cells by Western blot. Both of these cancer cells were treated with Notch inhibitor GSIs. The proliferation and apoptosis were observed after treated by GSI. ResultsNotch inhibitor and GSI suppressed the levels of Notch-1, Notch-2 and Notch-4, but not of Notch-3. GSI inhibited NPC cell proliferation by inducing apoptosis. In addition, GSI inhibited the AKT and MEK signaling in these NPC cells. ConclusionNPC cells may up-regulate Notch signaling to maintain their proliferation. Notch signaling pathway may be a new potential target for the treatment of NPC.

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