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Synergistic effect of PAF inhibition and X-ray irradiation in non-small cell lung cancer cells

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Abstract

Purpose

Proliferating cell nuclear antigen-associated factor (PAF) is involved in cancer cell growth and associated with cell death induced by ultraviolet (UV) radiation. However, the contribution of PAF to radiotherapy sensitivity in non-small cell lung cancer (NSCLC) is unknown. The aim of this study was to investigate the relationship between PAF expression and radiotherapy response in NSCLC.

Methods

Associations between PAF expression and patient survival outcomes were evaluated using publicly available online gene expression datasets. RNA interference was performed to knockdown PAF expression in the NSCLC cells. The effects of PAF knockdown on cell proliferation, migration, apoptosis, DNA damage, and activation of MEK/ERK and Wnt/β-catenin signaling pathways following X‑ray irradiation were evaluated in vitro.

Results

PAF was found to be overexpressed in lung cancer tissues compared with normal samples, and elevated PAF expression was significantly correlated with inferior patient survival. In vitro, knockdown of PAF inhibited cell proliferation, cell apoptosis, and migration induced by X‑ray irradiation. Moreover, X‑ray-induced intracellular DNA strand damage was more obvious following PAF knockdown. Additionally, PAF knockdown inhibited activation of the MEK/ERK and Wnt/β-catenin signaling pathways in X‑ray-irradiated A549 cells.

Conclusion

These data demonstrate that reduced expression of PAF enhances radiosensitivity in NSCLC cells. Mechanistically, inhibition of the MEK/ERK and Wnt/β-catenin signaling pathways caused by PAF interference may lead to impaired cell function and enhance sensitivity to X‑rays. Targeting PAF may therefore serve as a potential therapeutic strategy to increase the efficiency of radiotherapy in NSCLC patients, ultimately improving patient survival.

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Change history

  • 29 January 2021

    In the PDF the order of the email addresses of the corresponding authors was changed.

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Funding

This research project was supported by the National Natural Science Foundation of China (Grant No. 81402540; Grant No. 81672972) and the Medical and Health Science Foundation of Zhejiang Province (Grant No. 2018255396).

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Authors and Affiliations

  1. Zhejiang Key Laboratory of Radiation Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 310022, Hangzhou, Zhejiang, China

    Yamei Chen, Ying Jin, Hangjie Ying, Peng Zhang,  Ming Chen &  Xiao Hu

  2. Department of Medical Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 310022, Hangzhou, Zhejiang, China

    Ying Jin

  3. Department of Radiation Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 310022, Hangzhou, Zhejiang, China

    Ming Chen &  Xiao Hu

Authors
  1. Yamei Chen
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  2. Ying Jin
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  3. Hangjie Ying
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  4. Peng Zhang
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  5. Ming Chen
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  6. Xiao Hu
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Contributions

Conception and design: M Chen; administrative support: P Zhang; provision of study materials: X Hu; data analysis and interpretation: Y Chen, Y Jin; manuscript writing: all authors; final approval of manuscript: all authors.

Corresponding authors

Correspondence to Ming Chen or Xiao Hu.

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Conflict of interest

Y. Chen, Y. Jin, H. Ying, P. Zhang, M. Chen, and X. Hu declare that they have no competing interests.

Caption Electronic Supplementary Material

66_2020_1708_MOESM1_ESM.pdf

Supplementary Fig.1 Knockdown of PAF in H358 cells inhibits cell proliferation and enhances cell apoptosis in response to radiation.

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Chen, Y., Jin, Y., Ying, H. et al. Synergistic effect of PAF inhibition and X-ray irradiation in non-small cell lung cancer cells. Strahlenther Onkol 197, 343–352 (2021). https://doi.org/10.1007/s00066-020-01708-7

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  • DOI: https://doi.org/10.1007/s00066-020-01708-7

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