title: Knockdown of NFBD1/MDC1 enhances chemosensitivity to cisplatin or 5-fluorouracil in nasopharyngeal carcinoma CNE1 cells.
abstract: Nasopharyngeal carcinoma (NPC) is a rare but highly invasive cancer that is prevalent among people of southern Chinese ancestry in southern China and Southeast Asia. Radiotherapy and cisplatin (CDDP)-based chemotherapy are the main treatment options. Unfortunately, disease response to concurrent chemoradiotherapy varies among patients with NPC, and many cases are resistant to CDDP and radiotherapy. NFBD1 functions in cell cycle checkpoint activation and DNA repair following DNA damage. In this study, we identified the NFBD1 as a tractable molecular target to chemosensitize NPC cells. NFBD1 expression in NPC CNE1 cell lines was depleted using lentivirus-mediated short hairpin RNA, and the elevated sensitivity of these NFBD1-inhibited NPC cells to therapeutic reagent CDDP and 5-fluorouracil (5-FU) was evaluated using MTS assays. Flow cytometry analysis also showed that NFBD1 knockdown led to an obvious induction of apoptosis in CDDP- or 5-FU-treated CNE1 cells. Furthermore, we implicated the involvement of NFBD1 in Rad51 and DNA-PKcs foci formation following CDDP or 5-FU chemotherapy. In conclusion, NFBD1 knockdown improves the chemosensitivity of NPC cells by inhibiting cell growth and promoting apoptosis through the impairment of DNA damage repair, suggesting NFBD1 as a novel therapeutic target for NPC.
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Zuxia
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Houyong
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Suling
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research, China Center, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Youquan
authors.initials: Y
authors.lastname: Bu
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. hghcq@sina.com.
authors.forename: Guohua
authors.initials: G
authors.lastname: Hu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002277:Carcinoma; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C413163:MDC1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D002945:Cisplatin; D005472:Fluorouracil
keywords: Apoptosis; Chemosensitivity; DNA damage response; DNA double-strand breaks; NFBD1/MDC1; NPC