방사선의학 웹진

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Abstract

Tumor cell radioresistance is a major contributor to radiotherapy failure, highlighting the importance of identifying predictive biomarkers for radioresistance. In this work, we established a radioresistant H460 (RR-H460) cell line from parental radiosensitive H460 lung cancer cells by exposure to fractionated radiation. The radiation-resistant, anti-apoptotic phenotype of RR-H460 cell lines was confirmed by their enhanced clonogenic survival and increased expression of the radioresistance genes Hsp90 and Her-3. RR-H460 cells displayed characteristics of cancer stem-like cells (CSCs), including induction of the surface marker CD44 and stem cell markers Nanog, Oct4, and Sox2. RR-H460 cells also exhibited sphere formation and malignant behavior, further supporting a CSC phenotype. Using proteomic analyses, we identified 8 proteins that were up-regulated in RR-H460 CSC lines and therefore potentially involved in radioresistance and CSC-related biological processes. Notably, 4 of these-PAI-2, NOMO2, KLC4, and PLOD3-have not been previously linked to radioresistance. Depletion of these individual genes sensitized RR-H460 cells to radiotoxicity and additively enhancing radiation-induced apoptosis. Our findings suggest the possibility of integrating molecular targeted therapy with radiotherapy as a strategy for resolving the radioresistance of lung tumors. 

Author information

Yun HS1,2, Baek JH1,3, Yim JH1, Um HD1, Park JK1, Song JY1, Park IC1, Kim JS1, Lee SJ1, Lee CW3, Hwang SG1.

1a Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences , Seoul , South Korea.

2b Department of Life Science , College of Natural Sciences, Hanyang University , Seoul , South Korea.

3c Department of Molecular Cell Biology , Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine , Suwon , South Korea.