Open AccessDepletion of NFBD1/MDC1 Induces Apoptosis in Nasopharyngeal Carcinoma Cells Through the p53ROSMitochondrial Pathway
Author(s) -
Zhihai Wang,
Kui Liao,
Wenqi Zuo,
Xueliang Liu,
Qiu Zhili,
Zhongying Gong,
Chuan Liu,
Quan Zeng,
Yi Qian,
Liang Jiang,
Youquan Bu,
Suling Hong,
Guohua Hu
Publication year - 2017
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504016x14732772150226
Subject(s) - apoptosis , nasopharyngeal carcinoma , biology , cell culture , cancer research , downregulation and upregulation , gene silencing , dna damage , reactive oxygen species , transfection , tumor suppressor gene , cell growth , intracellular , microbiology and biotechnology , gene , dna , carcinogenesis , medicine , biochemistry , genetics , radiation therapy
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.