Zhou Lei, Chen Hong-Min, Qu Song, Li Ling, Zhao Wei, Liang Zhong-Guo, Yu Bin-Bin, Chen Kai-Hua, Lu Qi-Teng, Lin Guo-Xiang, Zhu Xiao-Dong
Department of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University and Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, P.R. China.
Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi, P.R. China.
Oncotarget. 2017 Dec 14;9(3):3230-3241. doi: 10.18632/oncotarget.23227. eCollection 2018 Jan 9.
Radioresistance is a major cause leads to treatment failure in nasopharyngeal carcinoma (NPC). In our previous study, we identified that QSOX1 is a differentially expressed protein in NPC cell lines with variable radiosensitivities. The present study aimed to investigate the biological behavior of QSOX1 in nasopharyngeal carcinoma (NPC) and its effect on radiosensitivity. The levels of QSOX1 detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in radioresistant NPC patient sera and tissue samples were markedly lower than those in radiosensitive samples. Small hairpin RNAs (shRNAs) were employed to knock down endogenous QSOX1 expression in CNE-2 cells, and then, radiosensitivity, apoptosis, migration and invasion were assessed using colony formation, Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays, respectively. Tumor growth and radioresistance were also evaluated using a xenograft model in nude mice. The shRNA-mediated knockdown of QSOX1 significantly increased cell survival under irradiation (IR) and weakened radiosensitivity, which was likely due to a reduction in the cell apoptosis rate after IR. Moreover, QSOX1 silencing led to the suppression of cellular migration and invasion. Similar results were obtained with the xenograft mouse model. Thus, targeting QSOX1 will provide a new avenue for increasing the sensitivity of NPC to radiotherapy.
放射抗性是导致鼻咽癌(NPC)治疗失败的主要原因。在我们之前的研究中,我们发现QSOX1是在具有不同放射敏感性的NPC细胞系中差异表达的蛋白质。本研究旨在探讨QSOX1在鼻咽癌(NPC)中的生物学行为及其对放射敏感性的影响。通过酶联免疫吸附测定(ELISA)和免疫组织化学(IHC)检测的放射抗性NPC患者血清和组织样本中QSOX1的水平明显低于放射敏感样本中的水平。使用小发夹RNA(shRNA)敲低CNE-2细胞中内源性QSOX1的表达,然后分别使用集落形成、细胞计数试剂盒-8(CCK-8)、流式细胞术和Transwell测定评估放射敏感性、细胞凋亡、迁移和侵袭。还使用裸鼠异种移植模型评估肿瘤生长和放射抗性。shRNA介导的QSOX1敲低显著增加了照射(IR)下的细胞存活并减弱了放射敏感性,这可能是由于IR后细胞凋亡率降低所致。此外,QSOX1沉默导致细胞迁移和侵袭受到抑制。在异种移植小鼠模型中也获得了类似的结果。因此,靶向QSOX1将为提高NPC对放疗的敏感性提供一条新途径。