Abstract 2008: Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholangiocarcinoma cell line

Abstract

Abstract Background: Histone deacetylase (HDAC) is well known to be associated with epigenetic regulation and carcinogenesis, and its inhibitors (HDACIs) induce the differentiation or apoptosis of cancer cells. Valproic acid (VPA) is one of the HDACIs, and it is clinically available as an oral antiepilepsy drug. We have reported that VPA augmented the anti-tumor effects of gemcitabine (GEM) in pancreas cancer cell lines and a cholangiocarcinoma cell line (2010 ASCO-GI), and we plan the clinical trial of combination therapy, S-1, that is a novel oral fluoropyrimidine derivative consisting of 5-fluorouracil (5-FU) prodrug tegafur, and VPA. We examined the augment effects of VPA with a combination of 5-FU in vitro. Methods: A human pancreas cancer cell line (SUIT-2) and a cholangiocarcinoma cell line (HuCCT1) were used. The anticancer effects of VPA combined with 5-FU in SUIT-2 and HuCCT1. The cell viability was evaluated by MTT assay. Results: Pancreas cancer cell line (SUIT-2): In 5-FU alone group, no effect of 5-FU was observed in dose of 1.0μM, and 17% and 30% of proliferation-inhibitory effects were observed in dose of 2.5 and 5.0μM, respectively. VPA (0.5mM) weakly suppressed cell viability by 13%. In combination of 5-FU and VPA, 19% of inhibitory effect was observed in dose of 5-FU 1.0μM/VPA 0.5mM, respectively. Cholangiocarcinoma cell line: 5-FU (1.0μM) did not suppress the cell viability, 5-FU (2.5μM) suppressed by 23%. VPA (0.5mM) did not suppress the cell viability, while VPA (1.0mM) weakly decreased it by 11%. 5-FU (1.0μM) and VPA (0.5mM) reduced by 30%, which significantly augmented the anticancer effect of 5-FU alone or VPA alone (P<0.01). Conclusion: VPA augmented the anti-tumor effect of 5-FU in both a pancreas cancer cell line and a cholangiocarcinoma cell line. Therefore, 5-FU plus VPA is suggested to be a promising therapeutic option for both pancreas cancer and cholangiocarcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2008. doi:10.1158/1538-7445.AM2011-2008