Chen Xuan, Wang Cong, Guan Shanghui, Liu Yuan, Han Lihui, Cheng Yufeng
Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Oncol Rep. 2016 Jul;36(1):239-46. doi: 10.3892/or.2016.4819. Epub 2016 May 18.
Telomerase is a type of reverse transcriptase that is overexpressed in almost all human tumor cells, but not in normal tissues, which provides an opportunity for radiosensitization targeting telomerase. Zidovudine, abacavir and lamivudine are reverse transcriptase inhibitors that have been applied in clinical practice for several years. We sought to explore the radiosensitization effect of these three drugs on human esophageal cancer cell lines. Eca109 and Eca9706 cells were treated with zidovudine, abacavir and lamivudine for 48 h before irradiation was administered. Samples were collected 1 h after irradiation. Clonal efficiency assay was used to evaluate the effect of the combination of these drugs with radiation doses of 2, 4, 6 and 8 Gy. DNA damage was measured by comet assay. Telomerase activity (TA) and relative telomere length (TL) were detected and evaluated by real-time PCR. Apoptosis rates were assessed by flow cytometric analysis. The results showed that all the drugs tested sensitized the esophageal squamous cell carcinoma (ESCC) cell lines to radiation through an increase in radiation-induced DNA damage and cell apoptosis, deregulation of TA and decreasing the shortened TL caused by radiation. Each of the drugs investigated (zidovudine, abacavir and lamivudine) could be used for sensitizing human esophageal cancer cell lines to radiation. Consequently, the present study supports the potential of these three drugs as therapeutic agents for the radiosensitization of esophageal squamous cell cancer.
端粒酶是一种逆转录酶，在几乎所有人类肿瘤细胞中均过度表达，但在正常组织中不表达，这为靶向端粒酶的放射增敏提供了机会。齐多夫定、阿巴卡韦和拉米夫定是已应用于临床实践数年的逆转录酶抑制剂。我们试图探究这三种药物对人食管癌细胞系的放射增敏作用。在进行照射前，用齐多夫定、阿巴卡韦和拉米夫定处理Eca109和Eca9706细胞48小时。照射后1小时收集样本。采用克隆效率测定法评估这些药物与2、4、6和8 Gy辐射剂量联合使用的效果。通过彗星试验测量DNA损伤。通过实时PCR检测并评估端粒酶活性（TA）和相对端粒长度（TL）。通过流式细胞术分析评估凋亡率。结果表明，所有测试药物均通过增加辐射诱导的DNA损伤和细胞凋亡、调节TA以及减少辐射引起的TL缩短，使食管鳞状细胞癌（ESCC）细胞系对辐射敏感。所研究的每种药物（齐多夫定、阿巴卡韦和拉米夫定）均可用于使人食管癌细胞系对辐射敏感。因此，本研究支持这三种药物作为食管鳞状细胞癌放射增敏治疗药物的潜力。
