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Published in: Strahlentherapie und Onkologie 4/2021

01-04-2021 | NSCLC | Original Article

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

Authors: Yamei Chen, Ying Jin, Hangjie Ying, Peng Zhang, Dr. Ming Chen, Dr. Xiao Hu

Published in: Strahlentherapie und Onkologie | Issue 4/2021

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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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Metadata
Title
Synergistic effect of PAF inhibition and X-ray irradiation in non-small cell lung cancer cells
Authors
Yamei Chen
Ying Jin
Hangjie Ying
Peng Zhang
Dr. Ming Chen
Dr. Xiao Hu
Publication date
01-04-2021
Publisher
Springer Berlin Heidelberg
Published in
Strahlentherapie und Onkologie / Issue 4/2021
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-020-01708-7

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