Abstract 589: DNA demethylating agent and histone deacetylation inhibitor synergistically induce paired box 5 gene expression in non-small cell lung cancer cell lines

Abstract

Abstract Epigenetic abnormalities play an important role in carcinogenesis and tumor suppressor paired box 5 gene (Pax5) is one of the most frequently methylated genes in non-small cell lung cancer (NSCLC). Depletion of Pax5 increased malignant characteristics including proliferation, migration and invasion in mammary cancer cells, while overexpression of Pax5 does not lead to cancer in vivo and induces apoptosis in hematological cancer cells. In this study, we found that Pax5 expression was frequently absent or down-regulated in NSCLC cell lines in vitro. We tested whether a combination of DNA demethylating agent Azacytidine and histone deacetylation (HDAC) inhibitor Vorinostat has a synergistic effect on the Pax 5 gene expression and cell growth inhibition of human NSCLC cell lines. We found that the combination induced Pax5 expression synergistically in NSCLC cell lines. Azacytidine decreased global DNA methylation and reduced CpG sites methylation rate in Pax5 promoter region. Vorinostat inhibited HDAC activity, but did not directly enhance the demethylation function of Azacytidine. Further investigation is needed to uncover the mechanism of action of the synergistic effect of these two agents on the Pax5 gene expression. Our results also show that different NSCLC cell lines respond similarly to the combination treatment under our experimental conditions. Citation Format: Yuanxin Liang, Roman Perez-Soler, Yiyu Zou. DNA demethylating agent and histone deacetylation inhibitor synergistically induce paired box 5 gene expression in non-small cell lung cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 589. doi:10.1158/1538-7445.AM2014-589