High expression of HIF-2α and its anti-radiotherapy effect in lung cancer stem cells

J.C. Sun, F. He, W. Yi, M.H. Wan, R. Li, X. Wei, R. Wu, D.L. Niu
2015 Genetics and Molecular Research  
Hypoxia-inducible factor-2 alpha (HIF-2α) has been shown to regulate cell stemness, although the expression and effects of HIF-2α in lung cancer stem cells remained unclear. This study investigated HIF-2α expression in lung cancer stem cells, as well as the relationship between HIF-2α expression and radioresistance in lung cancer cells. Stem-like cells (CD133 + ) in the non-small-cell lung cancer cell line A549 were enriched by serum-free culture conditions, and CD133 + cells were sorted via
more » ... were sorted via fluorescence-activated cell sorting. A549 cells were treated with middle-infrared radiation, and the level of HIF-2α expression was determined by a quantitative polymerase chain reaction assay and western blot analysis. The level of HIF-2α expression in tissue sections from 50 cases of clinically confirmed non-small-cell lung cancer was determined via immunohistochemical analysis, and its correlation with prognosis after radiotherapy was analyzed. HIF-2α levels in CD133 + cells were significantly higher than those in CD133cells (P = 0.032). However, after radiation treatment, these levels were significantly upregulated in both CD133 + and CD133cells (P = 0.031 and P = 0.023, respectively). After irradiation, the proportions of apoptotic, dead, and autophagic CD133 + A549 cells were 18111 HIF-2α and radioresistance in lung cancer stem cells ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 18110-18120 (2015) considerably lower than those of CD133 -A549 cells (P < 0.05). Furthermore, the recovery of carcinoembryonic antigen to pre-radiation levels was more rapid in lung cancer patients with high levels of HIF-2α expression, and these patients had shorter survival times (P = 0.018). HIF-2α is highly expressed in lung cancer stem cells, which may lead to radioresistance. In conclusion, HIF-2α is a potential prognostic marker for lung cancer.
doi:10.4238/2015.december.22.37 pmid:26782458 fatcat:v7fz2lym45aw7ngavgpas464o4