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Article Open Access

Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair

  • Authors:
    • Jun Dong
    • Yufeng Ren
    • Tian Zhang
    • Zhenyu Wang
    • Clifton C. Ling
    • Gloria C. Li
    • Fuqiu He
    • Chengtao Wang
    • Bixiu Wen
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Medical Physics and Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
    Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 912-920
    |
    Published online on: January 16, 2018
       https://doi.org/10.3892/or.2018.6217
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Abstract

The DNA-dependent protein kinase (DNA-PK) complex plays a pivotal role in non-homologous end-joining (NHEJ) repair. We investigated the mechanism of NU7441, a highly selective DNA-PK inhibitor, in NHEJ-competent mouse embryonic fibroblast (MEF) cells and NHEJ-deficient cells and explored the feasibility of its application in radiosensitizing nasopharyngeal carcinoma (NPC) cells. We generated wild-type and DNA-PKcs-/- MEF cells. Clonogenic survival assays, flow cytometry, and immunoblotting were performed to study the effect of NU7441 on survival, cell cycle, and DNA repair. NU7441 profoundly radiosensitized wild-type MEF cells and SUNE-1 cells, but not DNA-PKcs-/- MEF cells. NU7441 significantly suppressed radiation-induced DSB repair post-irradiation through unrepaired and lethal DNA damage, the cell cycle arrest. The effect was associated with the activation of cell cycle checkpoints. The present study revealed a mechanism by which inhibition of DNA-PK sensitizes cells to irradiation suggesting that radiotherapy in combination with DNA-PK inhibitor is a promising paradigm for the management of NPC which merits further investigation.
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Copy and paste a formatted citation
Spandidos Publications style
Dong J, Ren Y, Zhang T, Wang Z, Ling CC, Li GC, He F, Wang C and Wen B: Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair. Oncol Rep 39: 912-920, 2018.
APA
Dong, J., Ren, Y., Zhang, T., Wang, Z., Ling, C.C., Li, G.C. ... Wen, B. (2018). Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair. Oncology Reports, 39, 912-920. https://doi.org/10.3892/or.2018.6217
MLA
Dong, J., Ren, Y., Zhang, T., Wang, Z., Ling, C. C., Li, G. C., He, F., Wang, C., Wen, B."Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair". Oncology Reports 39.3 (2018): 912-920.
Chicago
Dong, J., Ren, Y., Zhang, T., Wang, Z., Ling, C. C., Li, G. C., He, F., Wang, C., Wen, B."Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair". Oncology Reports 39, no. 3 (2018): 912-920. https://doi.org/10.3892/or.2018.6217
Copy and paste a formatted citation
x
Spandidos Publications style
Dong J, Ren Y, Zhang T, Wang Z, Ling CC, Li GC, He F, Wang C and Wen B: Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair. Oncol Rep 39: 912-920, 2018.
APA
Dong, J., Ren, Y., Zhang, T., Wang, Z., Ling, C.C., Li, G.C. ... Wen, B. (2018). Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair. Oncology Reports, 39, 912-920. https://doi.org/10.3892/or.2018.6217
MLA
Dong, J., Ren, Y., Zhang, T., Wang, Z., Ling, C. C., Li, G. C., He, F., Wang, C., Wen, B."Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair". Oncology Reports 39.3 (2018): 912-920.
Chicago
Dong, J., Ren, Y., Zhang, T., Wang, Z., Ling, C. C., Li, G. C., He, F., Wang, C., Wen, B."Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair". Oncology Reports 39, no. 3 (2018): 912-920. https://doi.org/10.3892/or.2018.6217
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