RRC ID 18544
Author Iwahashi S, Ishibashi H, Utsunomiya T, Morine Y, Ochir TL, Hanaoka J, Mori H, Ikemoto T, Imura S, Shimada M.
Title Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholangiocarcinoma cell lines.
Journal J Med Invest
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.
Volume 58(1-2)
Pages 106-9
Published 2011-2-1
DOI 10.2152/jmi.58.106
PII JST.JSTAGE/jmi/58.106
PMID 21372494
MeSH Antineoplastic Combined Chemotherapy Protocols / therapeutic use Bile Duct Neoplasms / drug therapy* Bile Duct Neoplasms / pathology Bile Ducts, Intrahepatic* Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects Cholangiocarcinoma / drug therapy* Cholangiocarcinoma / pathology Fluorouracil / administration & dosage* Histone Deacetylase Inhibitors / administration & dosage* Humans Pancreatic Neoplasms / drug therapy* Pancreatic Neoplasms / pathology Valproic Acid / administration & dosage
Times Cited 37
Resource
Human and Animal Cells HuCCT1(RCB1960)