Effects of carbon-ion radiotherapy combined with a novel histone deacetylase inhibitor, cyclic hydroxamic-acid-containing peptide 31 in human esophageal squamous cell carcinoma.
BACKGROUND
Carbon-ion radiotherapy has several potential advantages over X-rays. This therapy has been applied for various solid tumors including esophageal squamous cell carcinoma (SCC). However, some patients have shown resistance to this treatment. A new effective combined treatment strategy is required for improving the therapeutic effects. Histone deacetylase inhibitors (HDACIs) are new therapeutic candidates for cancer treatment. Several studies have evaluated the combination of X-rays and HDACIs, but, to date, no study has evaluated carbon-ion radiotherapy combined with HDACIs.


METHODS
Radio-sensitization to carbon-ion radiotherapy when combined with a novel HDACI cyclic hydroxamic-acid-containing peptide 31(CHAP31) was assessed in human esophageal SCC both in vitro and in vivo. Changes of expression of genes related to DNA repair, by CHAP31 were assessed by quantitative real-time reverse transcriptional PCR analysis.


RESULTS
CHAP31 induced sensitization to carbon-ion radiotherapy in vitro and tumor growth was significantly suppressed by the combination of carbon-ion radiotherapy with CHAP31 in comparison to either agent alone in in vivo experiments. CHAP31 inhibited the expression of genes related to DNA repair.


CONCLUSIONS
CHAP31 sensitizes SCC cells to carbon-ion radiotherapy and this combinatory treatment may be a potentially useful therapeutic strategy for esophageal SCC.
Kano
Masayuki
M
Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chuoku, Chiba 260-0856, Japan. m_kano@graduate.chiba-u.jp
Yamada
Shigeru
S
Hoshino
Isamu
I
Murakami
Kentaro
K
Akutsu
Yasunori
Y
Sakata
Haruhito
H
Nishimori
Takanori
T
Usui
Akihiro
A
Miyazawa
Yukimasa
Y
Kamada
Tadashi
T
Tsujii
Hirohiko
H
Matsubara
Hisahiro
H
D000818:Animals; D002244:Carbon / Q000737:chemistry; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004260:DNA Repair / Q000235:genetics; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000532:radiotherapy*; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D063193:Heavy Ion Radiotherapy; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010456:Peptides, Cyclic / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; C505396:cyclic hydroxamic acid-containing peptide 31; D002244:Carbon