肿瘤预防与治疗2019，Vol.32Issue(1)：17-24,8.DOI:10. 3969／j. issn. 1674-0904. 2019. 01. 003
抑制内质网应激信号通路PERK-eIF2α介导NF-κB抑制口咽癌细胞增殖
Inhibition of Endoplasmic Reticulum Stress Signaling Pathway PERK-eIF2α Mediates NF-κB Inhibition of Oropharyngeal Cancer Cell Proliferation
摘要
Abstract
Objective: To explore the mechanism of regulation proliferation in oropharyngeal cancer cells by endoplasmic reticulum stress signaling pathway PERK-eIF2α. Methods: MTT assay was used to detect proliferation in oropharyngeal cancer cells (Fadu, Detroit 562) by different concentrations (0 μmmol／L, 1 μmmol／L, 10 μmmol／L, 50 μmmol／L) of PERK pathway inhibitor GSK2606414 and NF-κB inhibitor Bay11-7082. By Western Blot assay, we observed the activation of PERK-eIF2α-NF-κB signaling pathway. Cell apoptosis rate was detected by flow. Results: The results of MTT assay showed that with the increase of pretreatment concentration of GSK2606414, the survival rate of Fadu cells and Detroit 562 cells gradually decreased (F=56. 06, P=0. 000, F=71. 13, P=0. 000). Secondly, silencing PERK induced apoptosis. We further explored its mechanism and found that silencing PERK inhibits NF-κB phosphorylation, suggesting that abnormal activation of PERK-eIF2α signaling pathway induces NF-κB phosphorylation. Finally, we inhibited NF-κB to verify the above results. The results of MTT assay showed that with the in-crease of pretreatment concentration of Bay11 7082, the survival rate of Fadu cells and Detroit 562 cells decreased gradually (F=57. 48, P=0. 000, F=116. 76, P=0. 000). The apoptosis rate of Fadu cells and Detroit 562 cells in Bay11-7082 group was significantly higher than that in the control group (t=12. 38, 20. 88; P=0. 007, 0. 002). All of them showed in-hibition of cell proliferation and induced apoptosis. Conclusion: Inhibition of endoplasmic reticulum stress signaling pathway PERK-eIF2α mediates NF-κB inhibition of oropharyngeal cancer cell proliferation.关键词
内质网应激/PERK/eIF2α/NF-κB/口咽癌/增殖Key words
Endoplasmic reticulum stress/ PERK/ eIF2α/ NF-κB/ Oropharyngeal cancer/ Proliferation分类
医药卫生引用本文复制引用
Wang Jie,Zhang Miao,Lv Xintong,Qiao Qiao..抑制内质网应激信号通路PERK-eIF2α介导NF-κB抑制口咽癌细胞增殖[J].肿瘤预防与治疗,2019,32(1):17-24,8.基金项目
国家自然科学基金(编号:81402521) （编号:81402521）
北京市希思科临床肿瘤学研究基金(编号:YMT016-004) This study was supported by National Natural Science Foundation of China ( NO. 81402521) and Beijing CSCO Clinical Oncology Research Foundation (NO. YMT016-004). （编号:YMT016-004）
