title: Protein expression of nucleophosmin, annexin A3 and nm23-H1 correlates with human nasopharyngeal carcinoma radioresistancein vivo.
abstract: Radioresistance is a significant obstacle in the treatment of endemic nasopharyngeal carcinoma (NPC). The present study aimed to identify proteins associated with radioresistance in NPCin vitroandin vivo. Proteomics analyses were conducted to screen for differentially-expressed proteins (DEPs) in parental CNE-2 cells and CNE-2R cells. Using proteomics approaches, 16 DEPs were identified. Of these DEPs, nucleophosmin (NPM1), annexin A3 and nm23-H1, were verified using western blot analyses. The tumorigenicity was investigated using mouse xenograft tumorigenicity assays, and tumor growth curves were generated. The protein expression of NPM1, annexin A3 and nm23-H1 was examined by immunohistochemically staining tumor tissues. NPM1 and annexin A3 protein levels were downregulated in the CNE-2R cells, whereas nm23-H1 expression was upregulated.In vivotests showed that compared with the CNE-2 tumors, CNE-2R tumor growth was significantly retarded (P<0.05). CNE-2 tumor progression was inhibited by irradiation, but CNE-2R tumor progression was not, indicating that the CNE-2R cells were also radioresistantin vivo. NPM1 and annexin A3 expression was significantly lower in non-irradiated (NIR)-CNE-2R tumors compared with NIR-CNE-2 tumors (P<0.01). However, Nm23-H1 protein levels were significantly higher (P<0.05). Overall, the present study established comparable radioresistant and radiosensitive tumor models of human NPC, and identified candidate biomarkers that may correlate with radioresistance. The data showed that dysregulation of NPM1, annexin A3 and nm23-H1 expression correlated with the cellular and tumor radioresponse. These proteins are involved in the regulation of intracellular functions, including stress responses, cell proliferation and DNA repair. However, further clinical evaluations are required.
authors.affiliation: Department of Radiation Oncology, The Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China; Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Qu
authors.affiliation: Department of Radiation Oncology, The Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China; Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, The Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China; Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Zhong-Guo
authors.initials: ZG
authors.lastname: Liang
authors.affiliation: Department of Radiation Oncology, The Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China; Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, The Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China; Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Shi-Ting
authors.initials: ST
authors.lastname: Huang
authors.affiliation: Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China; Guangxi Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jia-Quan
authors.initials: JQ
authors.lastname: Li
authors.affiliation: Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China; Guangxi Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Dan-Rong
authors.initials: DR
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, The Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China; Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhu
keywords: animal model; nasopharyngeal neoplasms; protein expression; radioresistance; xenograft