title: TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinomain vitroandin vivo.
abstract: 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 ESCCin vitro, while the protein expression levels of AKT, phosphorylated (p)-AKT, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were evaluated by WBin vivo. 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 VEGFin vitroandin vivo. The present results suggested that TCN can effectively inhibit AKT, p-AKT, HIF-1α and VEGF, thus conferring radiosensitivity to ESCCin vitroandvivo. TCN is considered as an adjuvant in radiotherapy of ESCC in clinical application.
authors.affiliation: 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.
authors.forename: Qing
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Radiotherapy, People's Hospital of Jiangyin, Wuxi, Jiangsu 214400, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: He
authors.affiliation: 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.
authors.forename: Feng
authors.initials: F
authors.lastname: Shen
authors.affiliation: Department of Oncology, People's Hospital of Taizhou, Taizhou, Jiangsu 225300, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, Hubei Cancer Hospital, Wuhan, Hubei 430079, P.R. China.
authors.forename: Qu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Oncology, People's Hospital of Taizhou, Taizhou, Jiangsu 225300, P.R. China.
authors.forename: Jun-Xing
authors.initials: JX
authors.lastname: Huang
authors.affiliation: Department of Oncology, People's Hospital of Taizhou, Taizhou, Jiangsu 225300, P.R. China.
authors.forename: Zheng-Dong
authors.initials: ZD
authors.lastname: Wu
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xin-Chen
authors.initials: XC
authors.lastname: Sun
authors.affiliation: Department of Oncology, People's Hospital of Taizhou, Taizhou, Jiangsu 225300, P.R. China.
authors.forename: Sheng-Bin
authors.initials: SB
authors.lastname: Dai
keywords: AKT; ESCC; TCN; radiotherapy