X-radiation induces non-small-cell lung cancer apoptosis by upregulation of axin expression. International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] Journal article | | Title | X-radiation induces non-small-cell lung cancer apoptosis by upregulation of axin expression. | | Author(s) | Han Y, Wang Y, Xu HT, Yang LH, Wei Q, Liu Y, Zhang Y, Zhao Y, Dai SD, Miao Y, Yu JH, Zhang JY, Li G, Yuan XM, Wang EH | | Institution | Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital of China Medical University, Shenyang, PR China. | | Source | Int J Radiat Oncol Biol Phys 2009 Oct 1; 75(2):518-26. | | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19735876 |
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