X-Radiation Induces Non-Small-Cell Lung Cancer Apoptosis by Upregulation of Axin Expression
- Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital of China Medical University, Shenyang (China)
- Department of Radiation Oncology, First Affiliated Hospital of China Medical University, Shenyang (China)
Purpose: Axis inhibition (Axin) is an important negative regulator of the Wnt pathway. This study investigated the relationship between Axin expression and sensitivity to X-rays in non-small-cell lung cancer (NSCLC) to find a useful indicator of radiosensitivity. Methods and Materials: Tissue from NSCLC patients, A549 cells, and BE1 cells expressing Axin were exposed to 1-Gy of X-radiation. Axin and p53 expression levels were detected by immunohistochemistry and reverse transcription-PCR. Apoptosis was determined by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay and FACS (fluorescence-activate cell sorter) analysis. Caspase-3 activity was determined by Western blotting. Phospho-JNK expression was determined by immunofluorescence. Results: The expression of Axin was significantly lower in NSCLC tissues than in normal lung tissues (p < 0.05). Axin expression correlates with differentiation, TNM staging, and lymph node metastasis of NSCLC (p < 0.05). Its expression negatively correlates with the expression of p53(mt) (p=0.000) and positively correlates with apoptosis (p=0.002). The prognosis of patients with high expression of Axin was better than those with low expression. X-radiation increases Axin expression in NSCLC tissue, and caspase-3 is significantly higher in samples in which Axin is increased (p < 0.05). Both X-radiation and Axin induce apoptosis of A549 and BE1 cells; however, the combination of the two enhances the apoptotic effect (p < 0.05). In A549 cells, inhibition of p53 blocks Axin-induced apoptosis, whereas in BE1 cells, the JNK pathway is required. Conclusions: Axin induces the p53 apoptotic pathway in cells where this pathway is intact; however, in cells expressing p53(mt), Axin induces apoptosis via the JNK pathway. Elevated Axin expression following X-ray exposure is a reliable indicator for determining the radiosensitivity of NSCLC.
- OSTI ID:
- 21282056
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 75, Issue 2; Other Information: DOI: 10.1016/j.ijrobp.2009.05.040; PII: S0360-3016(09)00817-7; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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