title: X-radiation inhibits histone deacetylase 1 and 2, upregulates Axin expression and induces apoptosis in non-small cell lung cancer.
abstract: BACKGROUND
  Histone deacetylase (HDAC) plays an important role in the deacetylation of histone, which can alter gene expression patterns and affect cell behavior associated with malignant transformation. The aims of this study were to investigate the relationships between HDAC1, HDAC2, clinicopathologic characteristics, patient prognosis and apoptosis, to clarify the mechanism of upregulation of the Axis inhibitor Axin (an important regulator of the Wnt pathway) by X-radiation and to elucidate the effect of siRNA on radiation therapy of non-small cell lung cancer (NSCLC).
  
  
  METHODS
  HDAC1 and HDAC2 expression levels were measured by immunohistochemistry and reverse transcription PCR. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling and fluorescence activated cell sorting. BE1 cells expressing Axin were exposed to 2 Gy of X-radiation.
  
  
  RESULTS
  Expression of HDAC1 and that of HDAC2 were correlated, and significantly higher in NSCLC tissues than in normal lung tissues (P < 0.05). HDAC1 and HDAC2 expression was correlated with pTNM stage and negatively correlated with differentiation of NSCLC and apoptotic index (P < 0.05). The prognosis of patients with low expression of HDAC1 and HDAC2 was better than that of those with high expression. X-radiation and siRNA inhibited HDAC1 and HDAC2 expression in NSCLC cells and Axin levels were significantly higher in BE1 cells.
  
  
  CONCLUSIONS
  X-radiation and siRNA inhibit expression of HDAC1 and HDAC2, weaken the inhibitory effect of HDAC on Axin, upregulate Axin expression and induce apoptosis of lung cancer cells. Inhibition of HDAC1 and HDAC2 is a means of enhancing the radiosensitivity of NSCLC.
authors.affiliation: Department of Pathology, College of Basic Medical Sciences, First Affiliated Hospital of China Medical University, North 2nd Road 92, Heping Ward, Shenyang, 110001, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lian-he
authors.initials: LH
authors.lastname: Yang
authors.forename: Xiao-yi
authors.initials: XY
authors.lastname: Mi
authors.forename: Shun-dong
authors.initials: SD
authors.lastname: Dai
authors.forename: Qing-chang
authors.initials: QC
authors.lastname: Li
authors.forename: Hong-tao
authors.initials: HT
authors.lastname: Xu
authors.forename: Juan-han
authors.initials: JH
authors.lastname: Yu
authors.forename: Guang
authors.initials: G
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Chong
authors.initials: C
authors.lastname: Han
authors.forename: Xi-ming
authors.initials: XM
authors.lastname: Yuan
authors.forename: En-hua
authors.initials: EH
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D060466:Axin Protein / Q000378:metabolism*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D056464:Histone Deacetylase 2 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014965:X-Rays
chemical_list: C555451:AXIN1 protein, human; D060466:Axin Protein; D034741:RNA, Small Interfering; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2