Raltitrexed increases radiation sensitivity of esophageal squamous carcinoma cells
Raltitrexed increases radiation sensitivity of esophageal squamous carcinoma cells
复制标题
雷替曲塞增加食管鳞癌细胞的放射敏感性
DOI：
10.1186/s12935-019-0752-y
复制
发表时间：
2019-02-18
影响因子：
5.8
通讯作者：
Sun, Xin-chen
中科院分区：
文献类型：
--
作者：
Ding, Wen-Xiu;Liu, Shu;Sun, Xin-chen
背景放射治疗仍然是一种重要的治疗手段，特别是对于那些不适合根治性切除的患者。为了提高食道癌的放射敏感性，已开发了许多策略，并取得了一定的成功。方法本研究旨在探讨雷替曲塞是否能提高食管鳞癌的放射敏感性。用雷替曲塞或二甲基亚砜与人食管癌细胞株24 h孵育，并分别给予或不给予后续照射。细胞计数试剂盒检测细胞增殖，克隆存活实验检测细胞放射增敏作用。用流式细胞仪检测各组细胞凋亡率和细胞周期分布。免疫荧光分析检测DNA双链断裂。免疫印迹分析Bax、Cyclin B1、cdc2/pCDc2、cdc25C/pCDc25C等辐射信号转导相关蛋白的表达水平。结果表明，雷替曲塞通过增加辐射诱导的食管鳞癌细胞的DNA双链断裂、G2/M期停滞和辐射诱导的细胞凋亡，增强了细胞对辐射的敏感性。在TE-13细胞系中，雷替曲塞对ESCC细胞的增敏倍数为1.23~2.10。体外实验中，雷替曲塞对裸鼠的放射治疗效果也有一定的提高。这种抗代谢药物在未来食道癌同期放射治疗的临床试验中很有希望。
BackgroundRadiation therapy remains an important therapeutic modality, especially for those patients who are not candidates for radical resection. Many strategies have been developed to increase the radiosensitivity of esophageal cancer, with some success.MethodsThis study was conducted to determine whether raltitrexed can enhance radiosensitivity of esophageal squamous cell carcinoma (ESCC). ESCC cell lines 24 h were incubated with raltitrexed or DMSO with or without subsequent irradiation. Cell Counting Kit assay-8 assay and clonogenic survival assay were used to measure the cell proliferation and radiosensitization, respectively. Flow cytometry was utilized to examine cell apoptosis and cell cycle distribution in different groups. Immunofluorescence analysis was performed to detect deoxyribonucleic acid (DNA) double-strand breaks. In addition, the expression levels of proteins that are involved in radiation induced signal transduction including Bax, Cyclin B1, Cdc2/pCdc2, and Cdc25C/pCdc25C were examined by western blot analysis.ResultsThe results indicated that raltitrexed enhanced radiosensitivity of ESCC cells with increased DNA double-strand breaks, the G2/M arrest, and the apoptosis of ESCC cells induced by radiation. The sensitization enhancement ratio of 1.23–2.10 was detected for ESCC cells with raltitrexed treatment in TE-13 cell line. In vitro, raltitrexed also increased the therapeutic effect of radiation in nude mice.ConclusionRaltitrexed increases the radiosensitivity of ESCC. This antimetabolite drug is promising for future clinical trials with concurrent radiation in esophageal cancer.