title: X-radiation induces non-small-cell lung cancer apoptosis by upregulation of Axin expression.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital of China Medical University, Shenyang, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Xu
authors.forename: Lian-He
authors.initials: LH
authors.lastname: Yang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wei
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Shun-Dong
authors.initials: SD
authors.lastname: Dai
authors.forename: Yuan
authors.initials: Y
authors.lastname: Miao
authors.forename: Juan-Han
authors.initials: JH
authors.lastname: Yu
authors.forename: Jun-Yi
authors.initials: JY
authors.lastname: Zhang
authors.forename: Guang
authors.initials: G
authors.lastname: Li
authors.forename: Xi-Ming
authors.initials: XM
authors.lastname: Yuan
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D060466:Axin Protein; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011836:Radiation Tolerance / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D060466:Axin Protein; D014408:Biomarkers, Tumor; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D048670:MAP Kinase Kinase 4; D053148:Caspase 3