RSPO3 regulates the radioresistance of Non-Small cell lung cancer cells via NLRP3 Inflammasome-Mediated pyroptosis.

Autor: Li H; School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou 730050, China., Zhang J; School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou 730050, China., Yu B; Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730030, China., Yang T; School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou 730050, China., Liu B; Radiotherapy center, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, 730050, China., Li F; College of Life Sciences, Northwest Normal University, Lanzhou, 730070, China., Jin X; Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730030, China., Li Q; Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730030, China. Electronic address: liqiang@impcas.ac.cn.
Jazyk: angličtina
Zdroj: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology [Radiother Oncol] 2024 Nov; Vol. 200, pp. 110528. Date of Electronic Publication: 2024 Sep 07.
DOI: 10.1016/j.radonc.2024.110528
Abstrakt: Purpose: Radioresistance is a significant challenge in the radiotherapy of non-small cell lung cancer (NSCLC). This study aimed to investigate the role of R-spondin 3 (RSPO3) in regulating NSCLC radioresistance.
Methods and Materials: RNA sequencing was performed to analyze genes that are differentially expressed in radioresistant NSCLC cell lines. RSPO3 overexpression and knockdown experiments were conducted to assess its impact on radiosensitivity. The involvement of the β-catenin-NF-κB signaling pathway and the NLRP3 inflammasome in RSPO3-mediated radiosensitivity was also evaluated. In vivo experiments were conducted using a clinical-grade anti-RSPO3 antibody (OMP-131R10/rosmantuzumab) to assess its impact on radiation-induced pyroptosis and subsequent anti-tumor immunity.
Results: RSPO3 expression was downregulated in radioresistant NSCLC cells. Overexpression of RSPO3 increased NSCLC radiosensitivity through the induction of pyroptosis, which was mediated by the β-catenin-NF-κB signaling pathway and the NLRP3 inflammasome. The anti-RSPO3 antibody effectively blocked radiation-induced pyroptosis and anti-tumor immunity in vivo. Conversely, upregulation of RSPO3 enhanced NSCLC tumor radiosensitivity.
Conclusions: The findings demonstrated that RSPO3 plays a crucial role in regulating NSCLC radioresistance via NLRP3 mediated pyroptosis. Targeting the RSPO3-NLRP3 inflammasome axis may offer a potential therapeutic strategy to enhance the efficacy of radiotherapy for NSCLC patients.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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