摘要

Fractionated ionizing radiation (FIR) is a radiotherapy regimen that is regularly performed as part of lung cancer treatment. In contrast to the growth inhibition caused by DNA damage, immunomodulation in post-irradiated cancer cells is not well documented. Interferon (IFN)-γ confers anticancer activity by triggering both growth inhibition and cytotoxicity. This study investigated the priming effects of FIR with immunomodulation on the anticancer IFN-γ. Cell morphology, cell growth, and cytotoxicity were observed in FIR-treated A549 lung adenocarcinoma. Induction of p53 and epithelial-mesenchymal transition (EMT) were monitored. Following FIR, activation of IFN-γ signaling pathways were detected. FIR caused changes in cell morphology, inhibited cell growth, and induced cytotoxicity. While p53 was induced by FIR, no epithelial-mesenchymal transition could be found. Following IFN-γ stimulation, FIR-induced p53-associated cell cytotoxicity was significantly enhanced. Additionally, FIR increased the downstream response to IFN-γ by facilitating IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) signaling without affecting the receptor expression. FIR-facilitated STAT1 activation through the mechanism involving mitogen-activated protein kinase activation and Src-homology 2 domain-containing tyrosine phosphatase 2 inactivation. These results demonstrate the FIR-facilitated IFN-γ signaling and its anticancer activity.

原文英語
期刊Journal of Cellular Physiology
DOIs
出版狀態打印前電子出版 - 二月 14 2019

指紋

Ionizing radiation
Ionizing Radiation
Interferons
Cytotoxicity
STAT1 Transcription Factor
Epithelial-Mesenchymal Transition
Immunomodulation
Chemical activation
Cell growth
Growth
SH2 Domain-Containing Protein Tyrosine Phosphatases
Adenocarcinoma of lung
Oncology
Radiotherapy
Mitogen-Activated Protein Kinases
Phosphoric Monoester Hydrolases
Transcriptional Activation
DNA Damage
Tyrosine
Lung Neoplasms

引用此文

@article{6be22a60848149638e088de1e31e9c41,
title = "Fractionated ionizing radiation facilitates interferon-γ signaling and anticancer activity in lung adenocarcinoma cells",
abstract = "Fractionated ionizing radiation (FIR) is a radiotherapy regimen that is regularly performed as part of lung cancer treatment. In contrast to the growth inhibition caused by DNA damage, immunomodulation in post-irradiated cancer cells is not well documented. Interferon (IFN)-γ confers anticancer activity by triggering both growth inhibition and cytotoxicity. This study investigated the priming effects of FIR with immunomodulation on the anticancer IFN-γ. Cell morphology, cell growth, and cytotoxicity were observed in FIR-treated A549 lung adenocarcinoma. Induction of p53 and epithelial-mesenchymal transition (EMT) were monitored. Following FIR, activation of IFN-γ signaling pathways were detected. FIR caused changes in cell morphology, inhibited cell growth, and induced cytotoxicity. While p53 was induced by FIR, no epithelial-mesenchymal transition could be found. Following IFN-γ stimulation, FIR-induced p53-associated cell cytotoxicity was significantly enhanced. Additionally, FIR increased the downstream response to IFN-γ by facilitating IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) signaling without affecting the receptor expression. FIR-facilitated STAT1 activation through the mechanism involving mitogen-activated protein kinase activation and Src-homology 2 domain-containing tyrosine phosphatase 2 inactivation. These results demonstrate the FIR-facilitated IFN-γ signaling and its anticancer activity.",
keywords = "anticancer, FIR, lung cancer, signaling, IFN‐γ",
author = "Szu-Yuan Wu and Chia-Ling Chen and Po-Chun Tseng and Chi-Yun Chiu and Yung-En Lin and Chiou-Feng Lin",
note = "{\circledC} 2019 Wiley Periodicals, Inc.",
year = "2019",
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day = "14",
doi = "10.1002/jcp.28258",
language = "English",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",

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T1 - Fractionated ionizing radiation facilitates interferon-γ signaling and anticancer activity in lung adenocarcinoma cells

AU - Wu, Szu-Yuan

AU - Chen, Chia-Ling

AU - Tseng, Po-Chun

AU - Chiu, Chi-Yun

AU - Lin, Yung-En

AU - Lin, Chiou-Feng

N1 - © 2019 Wiley Periodicals, Inc.

PY - 2019/2/14

Y1 - 2019/2/14

N2 - Fractionated ionizing radiation (FIR) is a radiotherapy regimen that is regularly performed as part of lung cancer treatment. In contrast to the growth inhibition caused by DNA damage, immunomodulation in post-irradiated cancer cells is not well documented. Interferon (IFN)-γ confers anticancer activity by triggering both growth inhibition and cytotoxicity. This study investigated the priming effects of FIR with immunomodulation on the anticancer IFN-γ. Cell morphology, cell growth, and cytotoxicity were observed in FIR-treated A549 lung adenocarcinoma. Induction of p53 and epithelial-mesenchymal transition (EMT) were monitored. Following FIR, activation of IFN-γ signaling pathways were detected. FIR caused changes in cell morphology, inhibited cell growth, and induced cytotoxicity. While p53 was induced by FIR, no epithelial-mesenchymal transition could be found. Following IFN-γ stimulation, FIR-induced p53-associated cell cytotoxicity was significantly enhanced. Additionally, FIR increased the downstream response to IFN-γ by facilitating IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) signaling without affecting the receptor expression. FIR-facilitated STAT1 activation through the mechanism involving mitogen-activated protein kinase activation and Src-homology 2 domain-containing tyrosine phosphatase 2 inactivation. These results demonstrate the FIR-facilitated IFN-γ signaling and its anticancer activity.

AB - Fractionated ionizing radiation (FIR) is a radiotherapy regimen that is regularly performed as part of lung cancer treatment. In contrast to the growth inhibition caused by DNA damage, immunomodulation in post-irradiated cancer cells is not well documented. Interferon (IFN)-γ confers anticancer activity by triggering both growth inhibition and cytotoxicity. This study investigated the priming effects of FIR with immunomodulation on the anticancer IFN-γ. Cell morphology, cell growth, and cytotoxicity were observed in FIR-treated A549 lung adenocarcinoma. Induction of p53 and epithelial-mesenchymal transition (EMT) were monitored. Following FIR, activation of IFN-γ signaling pathways were detected. FIR caused changes in cell morphology, inhibited cell growth, and induced cytotoxicity. While p53 was induced by FIR, no epithelial-mesenchymal transition could be found. Following IFN-γ stimulation, FIR-induced p53-associated cell cytotoxicity was significantly enhanced. Additionally, FIR increased the downstream response to IFN-γ by facilitating IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) signaling without affecting the receptor expression. FIR-facilitated STAT1 activation through the mechanism involving mitogen-activated protein kinase activation and Src-homology 2 domain-containing tyrosine phosphatase 2 inactivation. These results demonstrate the FIR-facilitated IFN-γ signaling and its anticancer activity.

KW - anticancer

KW - FIR

KW - lung cancer

KW - signaling

KW - IFN‐γ

U2 - 10.1002/jcp.28258

DO - 10.1002/jcp.28258

M3 - Article

C2 - 30767202

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

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