title: Silencing NFBD1/MDC1 enhances the radiosensitivity of human nasopharyngeal cancer CNE1 cells and results in tumor growth inhibition.
abstract: NFBD1 functions in cell cycle checkpoint activation and DNA repair following ionizing radiation (IR). In this study, we defined the NFBD1 as a tractable molecular target to radiosensitize nasopharyngeal carcinoma (NPC) cells. Silencing NFBD1 using lentivirus-mediated shRNA-sensitized NPC cells to radiation in a dose-dependent manner, increasing apoptotic cell death, decreasing clonogenic survival and delaying DNA damage repair. Furthermore, downregulation of NFBD1 inhibited the amplification of the IR-induced DNA damage signal, and failed to accumulate and retain DNA damage-response proteins at the DNA damage sites, which leaded to defective checkpoint activation following DNA damage. We also implicated the involvement of NFBD1 in IR-induced Rad51 and DNA-dependent protein kinase catalytic subunit foci formation. Xenografts models in nude mice showed that silencing NFBD1 significantly enhanced the antitumor activity of IR, leading to tumor growth inhibition of the combination therapy. Our studies suggested that a combination of gene therapy and radiation therapy may be an effective strategy for human NPC treatment.
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: K
authors.initials: K
authors.lastname: Liao
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research, China Center, Chongqing Medical University, Chongqing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Bu
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: S
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: G
authors.initials: G
authors.lastname: Hu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002277:Carcinoma; D018797:Cell Cycle Proteins; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*; D015398:Signal Transduction; D047368:Tumor Burden / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; C508937:MDC1 protein, mouse; D034741:RNA, Small Interfering; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse