Salubrinal抑制射线诱导NF-κB活化增加口腔癌细胞凋亡

doi:10.3760/cma.j.issn.1004-4221.2020.02.007

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摘要目的探讨Salubrinal调控射线诱导口腔癌细胞凋亡的作用机制。方法构建放射抗拒口腔癌细胞KBR (4 Gy/次,7~10d 1次共4次);克隆形成实验检测Salubrinal预处理后口腔癌细胞放射敏感性;蛋白印迹法检测射线及Salubrinal调控口腔癌细胞NF-κB-HIF-1α信号通路及凋亡标志蛋白cleaved PARP的表达;Annexin V、PI染色、流式细胞仪检测凋亡分数。结果克隆形成实验示Salubrinal增加口腔癌细胞放射敏感性,KB及KBR细胞放射增敏比分别为1.19和1.24。蛋白印迹法结果示射线诱导口腔癌细胞NF-κB-HIF-1α细胞活化具有时间依赖性,而Salubrinal抑制射线诱导其异常活化。Salubrinal增加射线诱导口腔癌细胞凋亡标志蛋白cleaved PARP表达及凋亡指数,而NF-κB激活剂TNF-α逆转了这一作用,提示Salubrinal通过抑制NF-κB活化增加射线调控口腔癌细胞凋亡。进一步应用NF-κB抑制剂Bay11-7082同样增加射线诱导口腔癌细胞凋亡,KB及KBR细胞系Bay11-7082+IR组cleaved PARP的表达为2.67±0.26、1.91±0.17,IR组为2.1±0.16、1.44±0.15(P<0.05)。结论 Salubrinal抑制射线诱导NF-κB活化增加射线诱导口腔癌细胞凋亡进而调控口腔癌细胞放射敏感性。

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	王婕
	张妙
	李改艳
	吕欣桐
	乔俏

关键词 ： Salubrinal, NF-κB, 口腔癌细胞系, 凋亡, 放射敏感性

Abstract：Objective To explore the mechanism of the role of Salubrinal in regulating the radiation-induced apoptosis of oral cancer cells. Methods Radioresistant KBR cell line was constructed (4 Gy per fraction, every 7-10 d for 4 times). The radiosensitivity of oral cancer cells after Salubrinal pretreatment was measured by colony formation assay. The expression levels of NF-κB-HIF-1α signaling pathway and apoptosis biomarker cleaved PARP in oral cancer cells were measured by Western blot. The apoptosis rate was detected by Annexin V, PI staining and flow cytometry. Results Colony formation assay demonstrated that Salubrinal increased the radiosensitivity of oral cancer cells. The radiosensitization ratios of KB and KBR cells were 1.19 and 1.24. Western blot revealed that the activation of NF-κB-HIF-1α was time-dependent in the radiation-induced oral cancer cells, whereas Salubrinal inhibited the radiation-induced abnormal activation. In addition, Salubrinal increased the expression of apoptosis biomarker cleaved PARP and apoptosis index in radiation-induced oral cancer cells, whereas TNF-α, an activator of NF-κB, reversed the effect, suggesting that Salubrinal increased the apoptosis of radiation-induced oral cancer cells by suppressing the activation of NF-κB. Pretreatment of NF-κB inhibitor Bay11-7082 also increased the cell apoptosis. The expression levels of cleaved PARP of KB and KBR cell lines in the Bay11-7082+IR group were 2.67±0.26 and 1.91±0.17, significantly higher compared with 2.1±0.16 and 1.44±0.15 in the IR group (both P<0.05). Conclusion Salubrinal can aggravate the apoptosis of radiation-induced oral cancer cells by inhibiting the radiation-induced activation of NF-κB, thereby regulating the radiosensitivity of oral cancer cells.

Key words： Salubrinal NF-κB Oral cancer cell line Apoptosis Radiosensitivity

收稿日期: 2018-08-19

基金资助:国家自然科学基金(81402521);北京市希思科临床肿瘤学研究基金(YMT016-004)

通讯作者: 乔俏,Email:qiaojiang120@126.com

引用本文:

王婕,张妙,李改艳等. Salubrinal抑制射线诱导NF-κB活化增加口腔癌细胞凋亡[J]. 中华放射肿瘤学杂志, 2020, 29(2): 111-114.

Wang Jie,Zhang Miao,Li Gaiyan et al. Salubrinal increases the apoptosis of oral cancer cells by inhibiting radiation-induced activation of NF-κB[J]. Chinese Journal of Radiation Oncology, 2020, 29(2): 111-114.

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