title: IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer.
abstract: BACKGROUND
  IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of recombinant IL-23 protein on cellular proliferation were examined by MTT assay. Statistical analysis consisted of Student's t-test or one way analysis of variance (ANOVA) where groups in the experiment were three or more.
  
  
  RESULTS
  In a cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression was significantly elevated in patient tumour samples (p < 0.05). IL-23A expression is epigenetically regulated through histone post-translational modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL-23 significantly increased cellular proliferation in NSCLC cell lines.
  
  
  CONCLUSIONS
  These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine.
authors.affiliation: Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland. bairda@tcd.ie
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Baird
authors.forename: Jennifer
authors.initials: J
authors.lastname: Leonard
authors.forename: Krisha M
authors.initials: KM
authors.lastname: Naicker
authors.forename: Lisa
authors.initials: L
authors.lastname: Kilmartin
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Byrne
authors.forename: Steven G
authors.initials: SG
authors.lastname: Gray
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D015331:Cohort Studies; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D044127:Epigenesis, Genetic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D053759:Interleukin-23 / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D009367:Neoplasm Staging; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D056572:Histone Deacetylase Inhibitors; D053759:Interleukin-23; D003841:Deoxycytidine; D015254:DNA Modification Methylases; D000093542:Gemcitabine