Open Access

ARTICLE

Depletion of NFBD1/MDC1 Induces Apoptosis in Nasopharyngeal Carcinoma Cells Through the p53–ROS–Mitochondrial Pathway

Zhihai Wang^*, Kui Liao^†, Wenqi Zuo^*, Xueliang Liu^*, Zhili Qiu^*, Zhitao Gong^*, Chuan Liu^*, Quan Zeng^*, Yi Qian^*, Liang Jiang^*, Youquan Bu^‡, Suling Hong^*, Guohua Hu^*

* Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China
† Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China
‡ Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research, China Center, Chongqing Medical University, Chongqing, P.R. China

Oncology Research 2017, 25(1), 123-136. https://doi.org/10.3727/096504016X14732772150226

Abstract

NFBD1, a signal amplifier of the p53 pathway, is vital for protecting cells from p53-mediated apoptosis and the early phase of DNA damage response under normal culture conditions. Here we investigated its expression in patients with nasopharyngeal carcinoma (NPC), and we describe the biological functions of the NFBD1 gene. We found that NFBD1 mRNA and protein were more highly expressed in NPC tissues than in nontumorous tissues. To investigate the function of NFBD1, we created NFBD1-depleted NPC cell lines that exhibited decreased cellular proliferation and colony formation, an increase in their rate of apoptosis, and an enhanced sensitivity to chemotherapeutic agents compared with in vitro controls. However, N-acetyl cysteine (NAC) and downregulation of p53 expression could partially reverse the apoptosis caused by the loss of NFBD1. Further analysis showed that loss of NFBD1 resulted in increased production of intracellular reactive oxygen species (ROS) depending on p53, which subsequently triggered the mitochondrial apoptotic pathway. Using a xenograft model in nude mice, we showed that silencing NFBD1 also significantly inhibited tumor growth and led to apoptosis. Taken together, our data suggest that inhibition of NFBD1 in NPC could be therapeutically useful.

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