Establishment of radioresistant NCI-H460 cells and investigation of their sensitivity to RSL-3
10.13491/j.issn.1004-714X.2025.05.021
- VernacularTitle:NCI-H460辐射抗性细胞的构建及其对RSL-3敏感性分析
- Author:
Di ZHAO
1
;
Ying LI
1
;
Xinyu ZHANG
1
;
Xiaohui SUN
1
;
Chang XU
1
;
Qiang LIU
1
;
Yan WANG
1
Author Information
1. Institute of Radiation Medicine Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine Tianjin 300192, China.
- Publication Type:OriginalArticles
- Keywords:
Non-small cell lung cancer;
Radioresistance;
Ferroptosis;
RSL-3
- From:
Chinese Journal of Radiological Health
2025;34(5):758-763
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish radioresistant human non-small cell lung cancer NCI-H460R model cells and evaluate the sensitivity of these radioresistant cells to a ferroptosis inducer. Methods Radioresistant cell lines, designated as NCI-H460 R20Gy and NCI-H460 R116Gy, were generated by subjecting parental NCI-H460 cells to fractionated irradiation with varying cumulative doses. Both parental cells and the established radioresistant cell lines were each randomly divided into four groups and exposed to irradiation at 0, 2, 4, and 6 Gy, respectively. Successful establishment of the radioresistant cell lines was confirmed by colony formation assay. Subsequently, cells were treated with increasing concentrations of the ferroptosis inducer RSL-3 to assess differential sensitivity between parental and radioresistant cells to ferroptosis. Results In comparison to the parental NCI-H460 cells (D0WT=1.2), both NCI-H460 R116Gy and NCI-H460 R20Gy cells exhibited radioresistance, with NCI-H460 R116Gy demonstrating a stronger radioresistance (D0R116Gy=1.5) than NCI-H460 R20Gy (D0R20Gy=1.4). Furthermore, NCI-H460 R116Gy cells exhibited increased sensitivity to RSL-3 relative to the parental cells (P < 0.001), while NCI-H460 R20Gy cells did not display a significant difference in sensitivity to RSL-3. Conclusion Human non-small cell lung cancer cells with radioresistance induced by a high cumulative irradiation dose exhibit increased sensitivity to the glutathione peroxidase 4-specific ferroptosis inducer RSL-3. This finding provides an experimental basis for optimizing combined treatment regimens involving radiotherapy and RSL-3 for non-small cell lung cancer patients with radiotherapy resistance.