Effects of carbon-ion radiotherapy combined with a novel histone deacetylase inhibitor, cyclic hydroxamic-acid-containing peptide 31 in human esophageal squamous cell carcinoma.
Effects of carbon-ion radiotherapy combined with a novel histone deacetylase inhibitor, cyclic hydroxamic-acid-containing peptide 31 in human esophageal squamous cell carcinoma.
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发表时间：
2009-11
影响因子：
2
通讯作者：
M. Kano;S. Yamada;Isamu Hoshino;Kentaro Murakami;Y. Akutsu;H. Sakata;T. Nishimori;A. Usui;Y. Miyazawa;T. Kamada;H. Tsujii;H. Matsubara
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作者：
M. Kano;S. Yamada;Isamu Hoshino;Kentaro Murakami;Y. Akutsu;H. Sakata;T. Nishimori;A. Usui;Y. Miyazawa;T. Kamada;H. Tsujii;H. Matsubara
与x射线相比，碳离子放射治疗有几个潜在的优势。该疗法已应用于各种实体肿瘤，包括食管鳞状细胞癌（SCC）。然而，一些患者对这种治疗表现出耐药性。为了提高治疗效果，需要一种新的有效的联合治疗策略。组蛋白去乙酰化酶抑制剂（HDACIs）是癌症治疗的新候选药物。一些研究已经评估了x射线和HDACIs的结合，但是，到目前为止，还没有研究评估了碳离子放疗与HDACIs的结合。材料与方法在体外和体内研究了在人食管鳞状细胞癌中，与新型hdac环羟肟酸肽31（CHAP31）联合使用碳离子放疗的放射致敏性。通过实时定量逆转录PCR分析评估DNA修复相关基因CHAP31的表达变化。结果在体内实验中，与单独使用CHAP31相比，碳离子放疗与CHAP31联合使用可显著抑制肿瘤生长。CHAP31抑制DNA修复相关基因的表达。结论CHAP31可使SCC细胞对碳离子放疗增敏，这种联合治疗方法可能是治疗食管SCC的有效方法。
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. MATERIALS AND 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. CONCLUSION CHAP31 sensitizes SCC cells to carbon-ion radiotherapy and this combinatory treatment may be a potentially useful therapeutic strategy for esophageal SCC.