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

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 proliferationinhibitory
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.

The journal of medical investigation : http://medical.med.tokushima-u.ac.jp/jmi/index.html