机构：[1]Department of Interventional Radiology, the Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China[2]Department of Oncology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, China[3]Department of Medical Oncology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China[4]Department of Radiotherapy, Hubei Cancer Hospital, Wuhan, China
The current study tested the anti-hepatocellular carcinoma (HCC) cell activity of TIC10, a first-in-class small-molecule tumor necrosis (TNF)-related apoptosisinducing ligand (TRAIL) inducer. TIC10 exerted potent anti-proliferative and proapoptotic actions in primary and established human HCC cells. TIC10 blocked AktErk activation, leading to Foxo3a nuclear translocation, as well as TRAIL and death receptor-5 (DR5) transcription in HCC cells. We propose that DNA-PKcs is a major resistance factor of TIC10 possibly via inhibiting Foxo3a nuclear translocation. DNAPKcs inhibition, knockdown or mutation facilitated TIC10-induced Foxo3a nuclear translocation, TRAIL/DR5 expression and cell apoptosis. Reversely, exogenous DNAPKcs over-expression inhibited above actions by TIC10. In vivo, oral administration of TIC10 significantly inhibited HepG2 tumor growth in nude mice, which was further potentiated with Nu7026 co-administration. Thus, TIC10 shows promising anti-HCC activity, alone or together with DNA-PKcs inhibitors.
基金：
This work is supported by the National Natural Science Foundation (81472786, 81472305), and by the Suzhou Industrial Technology Innovation Project (SYSD2016094).
第一作者机构：[1]Department of Interventional Radiology, the Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Interventional Radiology, the Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China[2]Department of Oncology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, China
推荐引用方式(GB/T 7714)：
Long Cheng,Yuan-yuan Liu,Pei-Hua Lu,et al.Identification of DNA-PKcs as a primary resistance factor of TIC10 in hepatocellular carcinoma cells[J].ONCOTARGET.2017,8(17):28385-28394.doi:10.18632/oncotarget.16073.
APA：
Long Cheng,Yuan-yuan Liu,Pei-Hua Lu,Yi Peng,Qiang Yuan...&Xu-ming Bai.(2017).Identification of DNA-PKcs as a primary resistance factor of TIC10 in hepatocellular carcinoma cells.ONCOTARGET,8,(17)
MLA：
Long Cheng,et al."Identification of DNA-PKcs as a primary resistance factor of TIC10 in hepatocellular carcinoma cells".ONCOTARGET 8..17(2017):28385-28394
医学