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Inhibition of DNA-PKcs enhances radiosensitivity and increases the levels of ATM and ATR in NSCLC cells exposed to carbon ion irradiation

  • Authors:
    • Lina Yang
    • Yuanyuan Liu
    • Chao Sun
    • Xinrui Yang
    • Zhen Yang
    • Juntao Ran
    • Qiuning Zhang
    • Hong Zhang
    • Xinyu Wang
    • Xiaohu Wang
  • View Affiliations / Copyright

    Affiliations: Institute of Cell Biology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Heavy Ion Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, Gansu 730000, P.R. China, Department of Radiotherapy, Gansu Province Tumor Hospital, Lanzhou, Gansu 730005, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2856-2864
    |
    Published online on: September 18, 2015
       https://doi.org/10.3892/ol.2015.3730
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Abstract

Non-small cell lung cancer (NSCLC) exhibits radioresistance to conventional rays, due to its DNA damage repair systems. NSCLC may potentially be sensitized to radiation treatment by reducing those factors that continuously enhance the repair of damaged DNA. In the present study, normal lung fibroblast MRC‑5 and lung cancer A549 cells were treated with NU7026 and CGK733, which are inhibitors of the DNA‑dependent protein kinase catalytic subunit (PKcs) and ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3‑related (ATR), respectively, followed by exposure to X‑rays and carbon ion irradiation. The cytotoxic activity, cell survival rate, DNA damage repair ability, cell cycle arrest and apoptosis rate of the treated cells were analyzed with MTT assay, colony formation assay, immunofluorescence and flow cytometry, respectively. The transcription and translation levels of the ATM, ATR and DNA‑PKcs genes were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. The results indicated that the radiosensitivity and DNA repair ability of A549 cells were reduced, and the percentages of apoptotic cells and those arrested at the G2/M phase of the cell cycle were significantly increased, following ionizing radiation with inhibitor‑pretreatment. The expression levels of ATM, ATR, DNA‑PKcs and phosphorylated histone H2AX, a biomarker for DNA double‑strand breaks, were all upregulated at the transcriptional or translational level in A549 cells treated with carbon ion irradiation, compared with the control and X‑rays‑treated cells. In addition, the treatment with 5‑50 µM NU7026 or CGK733 did not produce any obvious cytotoxicity in MRC‑5 cells, and the effect of the DNA‑PKcs‑inhibitor on enhancing the radiosensitivity of A549 cells was stronger than that observed for the ATM and ATR‑inhibitor. These findings demonstrated a minor role for ATM and ATR in radiation‑induced cell death, since the upregulation of ATM and ATR did not rescue the A549 cells subjected to ionizing irradiation. Therefore, future studies on DNA-PKcs, ATM and ATR may lead to novel specific therapies that supplement general radiotherapy for the treatment of lung cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Yang L, Liu Y, Sun C, Yang X, Yang Z, Ran J, Zhang Q, Zhang H, Wang X, Wang X, Wang X, et al: Inhibition of DNA-PKcs enhances radiosensitivity and increases the levels of ATM and ATR in NSCLC cells exposed to carbon ion irradiation. Oncol Lett 10: 2856-2864, 2015.
APA
Yang, L., Liu, Y., Sun, C., Yang, X., Yang, Z., Ran, J. ... Wang, X. (2015). Inhibition of DNA-PKcs enhances radiosensitivity and increases the levels of ATM and ATR in NSCLC cells exposed to carbon ion irradiation. Oncology Letters, 10, 2856-2864. https://doi.org/10.3892/ol.2015.3730
MLA
Yang, L., Liu, Y., Sun, C., Yang, X., Yang, Z., Ran, J., Zhang, Q., Zhang, H., Wang, X., Wang, X."Inhibition of DNA-PKcs enhances radiosensitivity and increases the levels of ATM and ATR in NSCLC cells exposed to carbon ion irradiation". Oncology Letters 10.5 (2015): 2856-2864.
Chicago
Yang, L., Liu, Y., Sun, C., Yang, X., Yang, Z., Ran, J., Zhang, Q., Zhang, H., Wang, X., Wang, X."Inhibition of DNA-PKcs enhances radiosensitivity and increases the levels of ATM and ATR in NSCLC cells exposed to carbon ion irradiation". Oncology Letters 10, no. 5 (2015): 2856-2864. https://doi.org/10.3892/ol.2015.3730
Copy and paste a formatted citation
x
Spandidos Publications style
Yang L, Liu Y, Sun C, Yang X, Yang Z, Ran J, Zhang Q, Zhang H, Wang X, Wang X, Wang X, et al: Inhibition of DNA-PKcs enhances radiosensitivity and increases the levels of ATM and ATR in NSCLC cells exposed to carbon ion irradiation. Oncol Lett 10: 2856-2864, 2015.
APA
Yang, L., Liu, Y., Sun, C., Yang, X., Yang, Z., Ran, J. ... Wang, X. (2015). Inhibition of DNA-PKcs enhances radiosensitivity and increases the levels of ATM and ATR in NSCLC cells exposed to carbon ion irradiation. Oncology Letters, 10, 2856-2864. https://doi.org/10.3892/ol.2015.3730
MLA
Yang, L., Liu, Y., Sun, C., Yang, X., Yang, Z., Ran, J., Zhang, Q., Zhang, H., Wang, X., Wang, X."Inhibition of DNA-PKcs enhances radiosensitivity and increases the levels of ATM and ATR in NSCLC cells exposed to carbon ion irradiation". Oncology Letters 10.5 (2015): 2856-2864.
Chicago
Yang, L., Liu, Y., Sun, C., Yang, X., Yang, Z., Ran, J., Zhang, Q., Zhang, H., Wang, X., Wang, X."Inhibition of DNA-PKcs enhances radiosensitivity and increases the levels of ATM and ATR in NSCLC cells exposed to carbon ion irradiation". Oncology Letters 10, no. 5 (2015): 2856-2864. https://doi.org/10.3892/ol.2015.3730
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