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X-radiation induces non-small-cell lung cancer apoptosis by upregulation of Axin expression
Yang Han1, Yan Wang, Hong-Tao Xu
1Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital of China Medical University, Shenyang, PR 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.
Insights
Axis inhibition (Axin) expression is lower in non-small-cell lung cancer (NSCLC) and correlates with poor prognosis. Elevated Axin post-X-ray exposure enhances apoptosis, indicating its potential as a radiosensitivity marker in NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Axis inhibition (Axin) is a key negative regulator of the Wnt signaling pathway.
- Understanding Axin's role in cancer progression and treatment response is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the correlation between Axin expression and radiosensitivity in non-small-cell lung cancer (NSCLC).
- To identify Axin as a potential biomarker for predicting patient response to X-ray therapy.
Main Methods:
- Analysis of Axin and p53 expression in NSCLC tissues and cell lines (A549, BE1) using immunohistochemistry and RT-PCR.
- Assessment of apoptosis via TUNEL assay and FACS analysis.
- Measurement of caspase-3 activity and phospho-JNK expression.
Main Results:
- Lower Axin expression was observed in NSCLC tissues compared to normal lung tissues, correlating with advanced TNM staging and lymph node metastasis.
- Axin expression positively correlated with apoptosis and better patient prognosis.
- X-radiation increased Axin expression, leading to elevated caspase-3 activity and enhanced apoptosis, particularly when combined with Axin.
- Axin-induced apoptosis involved the p53 pathway in cells with intact p53 and the JNK pathway in cells with mutated p53 (p53(mt)).
Conclusions:
- Axin plays a dual role in apoptosis induction, utilizing the p53 pathway or the JNK pathway depending on p53 status.
- Elevated Axin expression following X-ray exposure serves as a reliable indicator of radiosensitivity in NSCLC.
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