Salubrinal increases the apoptosis of oral cancer cells by inhibiting radiation-induced activation of NF-Κb
10.3760/cma.j.issn.1004-4221.2020.02.007
- VernacularTitle: Salubrinal抑制射线诱导NF-κB活化增加口腔癌细胞凋亡
- Author:
Jie WANG
1
,
2
;
Miao ZHANG
1
;
Gaiyan LI
1
;
Xintong LYU
1
;
Qiao QIAO
1
Author Information
1. Department of Radiatherapy, the First Hospital of China Medical University, Shenyang 110001, China
2. Department of Radiation Oncology, Shanxi Cancer Hospital, Taiyuan 030013, China
- Publication Type:Journal Article
- Keywords:
Salubrinal;
NF-κ
B;
Oral cancer cell line;
Apoptosis;
Radiosensitivity
- From:
Chinese Journal of Radiation Oncology
2020;29(2):111-114
- CountryChina
- Language:Chinese
-
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.
