Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chuoku, Chiba 260-0856, Japan.
Anticancer Res. 2009 Nov;29(11):4433-8.
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.
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.
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.
CHAP31 sensitizes SCC cells to carbon-ion radiotherapy and this combinatory treatment may be a potentially useful therapeutic strategy for esophageal SCC.
碳离子放疗相对于 X 射线具有多种潜在优势。这种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。需要一种新的有效联合治疗策略来提高治疗效果。组蛋白去乙酰化酶抑制剂（HDACIs）是癌症治疗的新的治疗候选药物。已经有几项研究评估了 X 射线和 HDACIs 的联合应用，但迄今为止，尚无研究评估碳离子放疗与 HDACIs 的联合应用。
在体外和体内评估了新型 HDACI 环状羟肟酸肽 31（CHAP31）与碳离子放疗联合应用时对人食管 SCC 的放射增敏作用。通过定量实时逆转录聚合酶链反应分析评估 CHAP31 对与 DNA 修复相关基因表达的变化。
CHAP31 诱导 SCC 细胞对碳离子放疗的敏感性增加，与单独使用碳离子放疗或 CHAP31 相比，联合应用可显著抑制体内实验中的肿瘤生长。CHAP31 抑制与 DNA 修复相关的基因表达。
CHAP31 使 SCC 细胞对碳离子放疗敏感，这种联合治疗可能是治疗食管 SCC 的一种潜在有效治疗策略。
