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Updated: May 30, 2026

Assays for Validating Histone Acetyltransferase Inhibitors
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Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

Histone deacetylase inhibitor enhances the anti-tumor effect of gemcitabine: a special reference to gene-expression

Shuichi Iwahashi1, Mitsuo Shimada, Tohru Utsunomiya

  • 1Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.

Oncology Reports
|August 2, 2011
PubMed

Insights

Valproic acid (VPA) combined with gemcitabine (GEM) significantly enhances anticancer effects in cholangiocarcinoma. This combination therapy, particularly involving HLA-DRA, may modify cancer cell differentiation.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Histone deacetylase (HDAC) inhibitors are linked to epigenetic regulation and cancer.
  • Valproic acid (VPA) is a clinically used HDAC inhibitor with demonstrated anticancer properties.
  • Cholangiocarcinoma is a challenging cancer with limited treatment options.

Purpose of the Study:

  • To investigate the combined anticancer effects of VPA and gemcitabine (GEM) in human cholangiocarcinoma cells (HuCCT1).
  • To explore the underlying molecular mechanisms of this combination therapy using microarray analysis.

Main Methods:

  • Cell proliferation assays were used to assess the efficacy of VPA, GEM, and their combination.
  • Microarray analysis identified differentially expressed genes.
  • Ingenuity Pathway Analysis (IPA) and RT-PCR were employed to elucidate gene interactions and expression.

Main Results:

  • The combination of GEM (5 nM) and VPA (0.5 mM) significantly reduced cell proliferation by 23% compared to single agents (P<0.01).
  • Microarray analysis revealed 43 differentially expressed genes between GEM and GEM+VPA groups.
  • IPA identified a 'Cellular Development' network relevant to cancer cell differentiation, with HLA-DRA expression significantly upregulated by the combination therapy (P<0.01).

Conclusions:

  • VPA significantly augments the anticancer effects of GEM in cholangiocarcinoma.
  • The combination therapy enhances gene networks, potentially through the modification of cancer cell differentiation, with HLA-DRA as a key player.
  • This combination strategy holds promise for treating cholangiocarcinoma.

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