Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholangiocarcinoma cell lines

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  • Iwahashi Shuichi
    Department of Digestive Surgery and Transplantation, Institute of Health Biosciences, the University of Tokushima Graduate School These authors equally contributed to this study.
  • Ishibashi Hiroki
    Department of Digestive Surgery and Transplantation, Institute of Health Biosciences, the University of Tokushima Graduate School These authors equally contributed to this study.
  • Utsunomiya Tohru
    Department of Digestive Surgery and Transplantation, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Morine Yuji
    Department of Digestive Surgery and Transplantation, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Lkhaguva Ochir Tovuu
    Department of Digestive Surgery and Transplantation, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Hanaoka Jun
    Department of Digestive Surgery and Transplantation, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Mori Hiroki
    Department of Digestive Surgery and Transplantation, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Ikemoto Tetsuya
    Department of Digestive Surgery and Transplantation, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Imura Satoru
    Department of Digestive Surgery and Transplantation, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Shimada Mitsuo
    Department of Digestive Surgery and Transplantation, Institute of Health Biosciences, the University of Tokushima Graduate School

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Abstract

Background: Histone deacetylase (HDAC) is well known to be associated with tumorigenesis through epigenetic regulation, and its inhibitors (HDACIs) induce differentiation and apoptosis of tumor cells. We examined the therapeutic effects of valproic acid (VPA, a HDACI) with a combination of 5-fluorouracil (5-FU) in vitro. Methods: A human pancreas cancer cell line (SUIT-2) and a cholangiocarcinoma cell line (HuCCT1) were used. Cell viabilities were evaluated by a cell proliferation assay. We determined the anticancer effects of VPA combined with 5-FU in these cell lines. Results: Pancreas cancer (SUIT-2): No effect of 5-FU (1.0 µM) was observed, but 17% and 30% of proliferation-inhibitory effects were recognized in a dose of 2.5 or 5.0 µM, respectively. Cell viability was only weakly reduced by VPA (0.5 mM). However, in combination of 5-FU (1.0 µM) with VPA (0.5 mM), 19% of inhibitory effect was observed. Cholangiocarcinoma (HuCCT1): 5-FU (1.0 µM) did not suppress the cell viability, but 5-FU (2.5 µM) suppressed by 23%. VPA (0.5 mM) did not suppress the cell viability, while VPA (1.0 mM) weakly decreased it by 11%. Combination of 5-FU (1.0 µM) and VPA (0.5 mM) markedly reduced the cell viability by 30%. Conclusion: VPA augmented the anti-tumor effects of 5-FU in cancer cell lines. Therefore, a combination therapy of 5-FU plus VPA may be a promising therapeutic option for patients with pancreas cancer and cholangiocarcinoma. J. Med. Invest. 58: 106-109, February, 2011

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