The novel HDAC inhibitor OBP-801/YM753 enhances the effects of 5-fluorouracil with radiation on esophageal squamous carcinoma cells

Oncol Res. 2014;21(5):281-6. doi: 10.3727/096504014X13890370410249.

Abstract

Histone deacetylase (HDAC) inhibitors have been shown to enhance the effects of 5-fluorouracil (5-FU) against various cancer cells; however, no report has shown that an HDAC inhibitor may enhance the effects of 5-FU with radiation. Therefore, we investigated whether the novel HDAC inhibitor OBP-801/YM753 could enhance the effects of 5-FU with radiation on esophageal squamous carcinoma KYSE170 cells. The inhibition of the cell growth was significantly stronger with the combination of OBP-801/YM753 with 5-FU than with the 5-FU treatment only. Furthermore, inhibition of the colony formation was the most effective with the combined treatment of OBP-801/YM753, 5-FU, and radiation. Western blot analysis showed that OBP-801/YM753 suppressed the expression of thymidylate synthase induced by 5-FU. Therefore, this three-combined therapy is promising for patients with esophageal squamous carcinoma.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / radiation effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Chemoradiotherapy
  • Drug Synergism
  • Enzyme Induction / drug effects
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / radiotherapy*
  • Esophageal Squamous Cell Carcinoma
  • Fluorouracil / administration & dosage
  • Fluorouracil / pharmacology*
  • Histone Deacetylase Inhibitors / administration & dosage
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Peptides, Cyclic / administration & dosage
  • Peptides, Cyclic / pharmacology*
  • Thymidylate Synthase / biosynthesis

Substances

  • Histone Deacetylase Inhibitors
  • Peptides, Cyclic
  • YM753 compound
  • Thymidylate Synthase
  • Fluorouracil