Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
Lung Cancer. 2013 Jan;79(1):83-90. doi: 10.1016/j.lungcan.2012.10.003. Epub 2012 Oct 30.
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).
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.
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.
These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine.
IL-23 是 IL-6 超家族的一员，在癌症中发挥着关键作用。目前对于 IL-23 在非小细胞肺癌（NSCLC）中的作用知之甚少。
使用 RT-PCR 和染色质免疫沉淀（ChIP）技术检测 NSCLC 细胞和巨噬细胞中 IL-23 的水平、表观遗传调控以及各种药物（DNA 甲基转移酶抑制剂、组蛋白去乙酰化酶抑制剂和吉西他滨）对其表达的影响。通过 MTT 测定法检测重组 IL-23 蛋白对细胞增殖的影响。统计分析包括学生 t 检验或单因素方差分析（ANOVA），实验中的组为三个或更多。
在一组原发性非小细胞肺癌（NSCLC）肿瘤患者的样本中，IL-23A 的表达显著升高（p < 0.05）。IL-23A 的表达通过组蛋白翻译后修饰和 DNA CpG 甲基化进行表观遗传调控。吉西他滨是一种用于 NSCLC 一线治疗的化疗药物，也诱导了 IL-23A 的表达。重组 IL-23 显著增加了 NSCLC 细胞系的细胞增殖。
因此，这些结果可能对使用表观遗传靶向治疗或吉西他滨治疗 NSCLC 患者具有重要意义。
