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Knockdown of NFBD1/MDC1 enhances chemosensitivity to cisplatin or 5-fluorouracil in nasopharyngeal carcinoma CNE1 cells

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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.

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Acknowledgments

This work was supported by the Health Bureau of Chongqing (2013-2-013), the National Natural Science Foundation of China (No. 81470676 and 81271061) and the National Key Clinical Specialties Construction Program of China.

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Authors and Affiliations

  1. Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Quan Zeng, Zhihai Wang, Chuan Liu, Zhitao Gong, Li Yang, Liang Jiang, Zuxia Ma, Yi Qian, Yucheng Yang, Houyong Kang, Suling Hong & Guohua Hu

  2. Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research, China Center, Chongqing Medical University, Chongqing, 400016, China

    Youquan Bu

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  1. Quan Zeng
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Zeng, Q., Wang, Z., Liu, C. et al. Knockdown of NFBD1/MDC1 enhances chemosensitivity to cisplatin or 5-fluorouracil in nasopharyngeal carcinoma CNE1 cells. Mol Cell Biochem 418, 137–146 (2016). https://doi.org/10.1007/s11010-016-2739-5

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