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Synergistic effect of PAF inhibition and X-ray irradiation in non-small cell lung cancer cells.
Chen, Yamei; Jin, Ying; Ying, Hangjie; Zhang, Peng; Chen, Ming; Hu, Xiao.
Afiliação
  • Chen Y; 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.
  • Jin Y; 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.
  • Ying H; 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.
  • Zhang P; 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.
  • Chen M; 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.
  • Hu X; 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. chenming@zjcc.org.cn.
Strahlenther Onkol ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33231712
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/ß-catenin signaling pathways following X­ray 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 X­ray irradiation. Moreover, X­ray-induced intracellular DNA strand damage was more obvious following PAF knockdown. Additionally, PAF knockdown inhibited activation of the MEK/ERK and Wnt/ß-catenin signaling pathways in X­ray-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/ß-catenin signaling pathways caused by PAF interference may lead to impaired cell function and enhance sensitivity to X­rays. Targeting PAF may therefore serve as a potential therapeutic strategy to increase the efficiency of radiotherapy in NSCLC patients, ultimately improving patient survival.
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Assunto da revista: Neoplasias / Radioterapia Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Assunto da revista: Neoplasias / Radioterapia Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China