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Radiosensitization of NSCLC cells to X-rays and carbon ions by the CHK1/CHK2 inhibitor AZD7762, Honokiol and Tunicamycin

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Abstract

Although radiotherapy, especially carbon-ion radiotherapy, is an effective treatment modality against non-small-cell lung cancer (NSCLC), studies using radiation combined with sensitizer for improving the efficacy of radiotherapy are still needed. In this work, we aimed to investigate in NSCLC A549 and H1299 cell lines the effects of different linear energy transfer (LET) radiations combined with diverse sensitizing compounds. Cells pretreated with the CHK1/CHK2 inhibitor AZD7762, Honokiol or Tunicamycin were irradiated with low-LET X-rays and high-LET carbon ions. Cell survival was assessed using the clonogenic cell survival assay. Cell cycle distribution and apoptosis were measured with flow cytometry, and DNA double strand break (DSB) and repair were detected using γ-H2AX immunofluorescence staining. Our results revealed that AZD7762, Honokiol and Tunicamycin demonstrated low cytotoxicity to NSCLC cells and a pronounced radiosensitizing effect on NSCLC cells exposed to carbon ions than X-rays. Unrepaired DNA DSB damages, the abrogation of G2/M arrest induced by irradiation, and finally apoptotic cell death were the main causes of the radiosensitizing effect. Thus, our data suggest that high-LET carbon ion combined with these compounds may be a potentially effective therapeutic strategy for locally advanced NSCLC.

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Acknowledgements

This work is jointly supported by the National Key Research Program of China (Grant Nos. 2016YFC0904700, 2016YFC0904702), The National Natural Science Foundation of China (Grant Nos. 11875299, U1532264), National Natural Science Foundation of China Academy of Engineering Physics (Grant Nos. U1730133), The Natural Science Foundation of Gansu Province (Grant Nos. 17JRSRA310).

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Authors and Affiliations

  1. Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou, 730000, Gansu, China

    Bingtao Liu, Weiqiang Chen, Hongbin Li, Feifei Li, Xiaodong Jin & Qiang Li

  2. Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, 730000, China

    Bingtao Liu, Weiqiang Chen, Hongbin Li, Feifei Li, Xiaodong Jin & Qiang Li

  3. Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou, 730000, Gansu, China

    Bingtao Liu, Weiqiang Chen, Hongbin Li, Feifei Li, Xiaodong Jin & Qiang Li

  4. University of Chinese Academy of Sciences, Beijing, 100049, China

    Bingtao Liu, Weiqiang Chen, Hongbin Li, Feifei Li, Xiaodong Jin & Qiang Li

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  1. Bingtao Liu
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Liu, B., Chen, W., Li, H. et al. Radiosensitization of NSCLC cells to X-rays and carbon ions by the CHK1/CHK2 inhibitor AZD7762, Honokiol and Tunicamycin. Radiat Environ Biophys 59, 723–732 (2020). https://doi.org/10.1007/s00411-020-00867-6

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