The Homologous Recombination Repair Pathway is Associated with Resistance to Radiotherapy in Nasopharyngeal Carcinoma

Autor: Zhihai Wang, Tao Lu, Yanshi Li, Quan Zeng, Guohua Hu, Wenqi Zuo, Youquan Bu
Rok vydání: 2020
Předmět:
Adult
Male
Adolescent
Blotting
Western
Fluorescent Antibody Technique
Biology
DNA damage response
Applied Microbiology and Biotechnology
homologous recombination repair
Histones
Young Adult
03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor
Radioresistance
otorhinolaryngologic diseases
medicine
Humans
NFBD1/MDC1
Radiosensitivity
Molecular Biology
Ecology
Evolution
Behavior and Systematics
Aged
030304 developmental biology
0303 health sciences
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms
Cell Biology
Middle Aged
Flow Cytometry
medicine.disease
Immunohistochemistry
Gene Expression Regulation
Neoplastic
radioresistance
Blot
stomatognathic diseases
Nasopharyngeal carcinoma
Cell culture
Cancer research
Female
Comet Assay
Signal transduction
Homologous recombination
DNA Damage
Research Paper
Developmental Biology
Zdroj: International Journal of Biological Sciences
ISSN: 1449-2288
Popis: Radiotherapy plays a major role in the management of nasopharyngeal carcinoma (NPC). However, the radioresistant cells limit its efficiency and drive recurrence inside the irradiated tumor volume leading to poor outcome for patients. To illuminate the signal pathway involved in the radioresistance and evaluate the potential for predicting NPC response to radiotherapy, we established the radioresistant NPC cell line (CNE2-RR) derived from NPC cell line CNE2 by gradually increased the radiation dose (total 60 Gy), and the radioresistance of CNE2-RR cells was evaluated by the colony formation, FCM and comet assays. Furthermore, comparison of established CNE2-RR cell line to parental cell line found the homologous recombination repair (HRR) proteins differences involved in NPC radioresistance. In addition, the differentially expressed proteins were further validated by western blotting, immunofluorescence and IHC in tumor xenografs and radioresistant NPC tissues. Furthermore, the correlation of HRR proteins expression levels with NPC radioresistance were evaluated. The results showed that the upregulation of HRR proteins were significantly correlated with NPC radioresistance. In addition, using the Youden Index cutoff value, a panel of the HRR proteins analyses revealed a sensitivity of 70%, specificity of 72%. Furthermore, silencing NFBD1 enhanced the radiosensitivity of CNE2-RR cells by impairing IR-inducing γ-H2AX and HR proteins foci formation. These results suggest that controlling the HRR signaling pathway may hold promise to overcome NPC radioresistance.
Databáze: OpenAIRE
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