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.
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 patienttumour 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 NSCLCpatients with either epigenetic targeted therapies or Gemcitabine.
Authors: Marta Usó; Eloísa Jantus-Lewintre; Silvia Calabuig-Fariñas; Ana Blasco; Eva García Del Olmo; Ricardo Guijarro; Miguel Martorell; Carlos Camps; Rafael Sirera Journal: Oncoimmunology Date: 2016-12-07 Impact factor: 8.110
Authors: Michele W L Teng; Edward P Bowman; Joshua J McElwee; Mark J Smyth; Jean-Laurent Casanova; Andrea M Cooper; Daniel J Cua Journal: Nat Med Date: 2015-06-29 Impact factor: 53.440
Authors: Anne-Marie Baird; Eilis Dockry; Anne Daly; Emma Stack; Derek G Doherty; Kenneth J O'Byrne; Steven G Gray Journal: Front Oncol Date: 2013-06-19 Impact factor: 6.244
Authors: Zhihong Yuan; Hiren J Mehta; Kamal Mohammed; Najmunissa Nasreen; Robert Roman; Mark Brantly; Ruxana T Sadikot Journal: PLoS One Date: 2014-05-19 Impact factor: 3.240