The novel HDAC inhibitor OBP-801/YM753 enhances the effects of 5-fluorouracil with radiation on esophageal squamous carcinoma cells.
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.
Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan.
Akinobu
A
Furutani
Yoshihiro
Y
Sowa
Hitoshi
H
Fujiwara
Eigo
E
Otsuji
Toshiyuki
T
Sakai
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D048708:Cell Growth Processes / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D000077277:Esophageal Squamous Cell Carcinoma; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D013940:Thymidylate Synthase / Q000096:biosynthesis; D047630:Depsipeptides
D005472:Fluorouracil; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; D013940:Thymidylate Synthase; C528967:YM753 compound; D047630:Depsipeptides