Abstract
The management of advanced nasopharyngeal carcinoma (NPC) remains a challenge. The ubiquitous nature of Epstein-Barr virus (EBV) infection in nonkeratinizing NPC has forced us to investigate novel drugs for NPC in the presence of EBV. In this study, we performed a small-scale screening of a library of compounds that target epigenetic regulators in paired EBV-positive and EBV-negative NPC cell lines. We found that bromodomain and extra-terminal (BET) inhibitor JQ1 preferentially inhibits the growth of EBV-positive NPC cells. JQ1 induces apoptosis, decreases cell proliferation and enhances the radiosensitivity in NPC cells, especially EBV-positive cells. Significantly, JQ1-induced cell death is c-Myc-dependent. Notably, RNA-seq analysis demonstrated that JQ1 represses TP63, TP53 and their targets. JQ1 also lessens the expression of PD-L1 in NPC. Moreover, the high potency of JQ1 in NPC cells was further confirmed in vivo in CNE2-EBV+ tumor-bearing mice. These findings indicate that JQ1 is a promising therapeutic candidate for advanced NPC.
Original language | English (US) |
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Article number | 761 |
Journal | Cell Death and Disease |
Volume | 9 |
Issue number | 7 |
DOIs | |
State | Published - Jul 1 2018 |
ASJC Scopus subject areas
- Immunology
- Cellular and Molecular Neuroscience
- Cell Biology
- Cancer Research