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Salubrinal increases the apoptosis of oral cancer cells by inhibiting radiation-induced activation of NF-κB
Wang Jie1,2, Zhang Miao1, Li Gaiyan1, Lyu Xintong1, Qiao Qiao1
1Department of Radiatherapy,the First Hospital of China Medical University,Shenyang 110001,China; 2Department of Radiation Oncology,Shanxi Cancer Hospital,Taiyuan 030013,China
AbstractObjective 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.
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.
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.