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Niclosamide sensitizes nasopharyngeal carcinoma to radiation by downregulating Ku70/80 expression

Authors :
Danxian Jiang
Dechao Zhan
Haiwen Li
Zihong Chen
Zhonghua Yu
Jun Yang
Hechao Zhou
Yin Yu
Zumin Xu
Jingjing Li
Mei Xiang
Yufang Zuo
Hai-Qing Luo
Source :
Journal of Cancer
Publication Year :
2018
Publisher :
Ivyspring International Publisher, 2018.

Abstract

The aim of the present study was to investigate whether niclosamide could sensitize the nasopharyngeal carcinoma cells to radiation and further explore the underlying mechanisms. CCK-8 assay was used to determine the effect of niclosamide on the proliferation of NPC cells. Colony formation assay was used to evaluate the radiosensitizing effect of niclosamide on NPC cells. Flow cytometry analysis was used to determine the apoptosis of NPC cells induced by niclosamide. Immunofluorescent staining was used to detect the formation of γ-H2AX foci and the localization of Ku70/80 proteins in NPC cells. Real-time PCR quantification analysis was used to examine the level of Ku70/80 mRNA. DNA damage repair-related proteins were detected by western blot analysis. Our results showed that niclosamide markedly suppressed the proliferation of NPC cells. Niclosamide pretreatment followed by irradiation reduced the colony forming ability of NPC cells. Niclosamide in combination with irradiation significantly increased the apoptotic rate of NPC cells. Niclosamide significantly reduced the transcriptional level of K70/80 but not the translocation of Ku70/80 protein induced by irradiation. In conclusion, our study demonstrated that niclosamide could inhibit the growth of NPC cells and sensitize the NPC cells to radiation via suppressing the transcription of Ku70/80.

Details

ISSN :
18379664
Volume :
9
Database :
OpenAIRE
Journal :
Journal of Cancer
Accession number :
edsair.doi.dedup.....248b50613b8f2607a67e3441a87cf7f4
Full Text :
https://doi.org/10.7150/jca.20963