J Cancer 2018; 9(4):736-744. doi:10.7150/jca.20963
Niclosamide sensitizes nasopharyngeal carcinoma to radiation by downregulating Ku70/80 expression
Cancer Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong Province, China.
* These authors have contributed equally to this study.
Li J, Li H, Zhan D, Xiang M, Yang J, Zuo Y, Yu Y, Zhou H, Jiang D, Luo H, Chen Z, Yu Z, Xu Z. Niclosamide sensitizes nasopharyngeal carcinoma to radiation by downregulating Ku70/80 expression. J Cancer 2018; 9(4):736-744. doi:10.7150/jca.20963. Available from http://www.jcancer.org/v09p0736.htm
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.
Keywords: niclosamide, nasopharyngeal carcinoma, radiosensitization, DNA damage repair, Ku70/80