Guo Qing, He Jia, Shen Feng, Zhang Wei, Yang Xi, Zhang Chi, Zhang Qu, Huang Jun-Xing, Wu Zheng-Dong, Sun Xin-Chen, Dai Sheng-Bin
Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China; Department of Oncology, People's Hospital of Taizhou, Taizhou, Jiangsu 225300, P.R. China.
Department of Radiotherapy, People's Hospital of Jiangyin, Wuxi, Jiangsu 214400, P.R. China.
Oncol Lett. 2017 Feb;13(2):949-954. doi: 10.3892/ol.2016.5515. Epub 2016 Dec 20.
The aim of the present study was to investigate the radiosensitization effect of triciribine (TCN) on human esophageal squamous cell carcinoma (ESCC) in normoxia or hypoxia and its mechanism. The cytotoxicity and radiosensitization mechanism of TCN were investigated by Cell Counting Kit 8, clonogenic assay, flow cytometry, western blotting (WB) and immunofluorescence staining of phospho-histone H2A.X, Ser139 (γ-H2AX) in ESCC , while the protein expression levels of AKT, phosphorylated (p)-AKT, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were evaluated by WB . The cytotoxicity of TCN was dose dependent. Upon exposure to TCN, ESCC cells in hypoxia treated with 4-Gy radiotherapy exhibited an evidently higher apoptotic rate than cells subjected to other treatments. TCN could significantly inhibit the protein expression of p-AKT, HIF-1α and VEGF and . The present results suggested that TCN can effectively inhibit AKT, p-AKT, HIF-1α and VEGF, thus conferring radiosensitivity to ESCC and . TCN is considered as an adjuvant in radiotherapy of ESCC in clinical application.
本研究的目的是探讨三氮脒（TCN）在常氧或缺氧条件下对人食管鳞状细胞癌（ESCC）的放射增敏作用及其机制。通过细胞计数试剂盒8、克隆形成试验、流式细胞术、蛋白质印迹法（WB）以及对ESCC中磷酸化组蛋白H2A.X（Ser139）（γ-H2AX）的免疫荧光染色来研究TCN的细胞毒性和放射增敏机制，同时通过WB评估AKT、磷酸化（p）-AKT、缺氧诱导因子（HIF）-1α和血管内皮生长因子（VEGF）的蛋白质表达水平。TCN的细胞毒性呈剂量依赖性。在接受4 Gy放疗的情况下，缺氧处理的ESCC细胞暴露于TCN后，其凋亡率明显高于接受其他处理的细胞。TCN可显著抑制p-AKT、HIF-1α和VEGF的蛋白质表达。目前的结果表明，TCN可有效抑制AKT、p-AKT、HIF-1α和VEGF，从而赋予ESCC放射敏感性。在临床应用中，TCN被认为是ESCC放射治疗的一种辅助药物。
