Bromodomain and extraterminal domain
proteins, especially bromodomain‑containing
protein 4 (Brd4), have recently emerged as therapeutic targets for several
cancers, although the role and mechanism of Brd4 in
glioblastoma multiforme (GBM) are unclear. In this study, we aimed to explore the underlying mechanisms of the anti‑tumor effects of Brd4 and the bromodomain inhibitor JQ1 on
glioma stem cells (GSCs). In vitro, JQ1 and small interfering RNAs targeting Brd4 (siBrd4) inhibited the proliferation and self‑renewal of GSCs. In vivo, JQ1 significantly inhibited the growth of xenograft GSCs
tumors. The RNA‑seq analysis revealed that the PI3K‑AKT pathway played an important role in GBM.
Vascular endothelial growth factor (
VEGF) and
VEGF receptor 2 phosphorylation was downregulated by exposure to JQ1 in GSCs, thereby reducing PI3K and AKT activity. In addition, treatment with JQ1 inhibited
MMP expression, thereby inhibiting degradation of the extracellular matrix by
MMP and angiogenesis in GBM
tumors. Suppression of AKT phosphorylation inhibited the expression of the
retinoblastoma/E2F1 complex, resulting in cell cycle arrest. In addition, treatment with siBrd4 or JQ1 induced apoptosis by activating AKT downstream target genes involved in apoptosis. In conclusion, these results suggest that Brd4 has great potential as a therapeutic target, and JQ1 has notable anti‑tumor effects against GBM which may be mediated via the
VEGF/PI3K/AKT signaling pathway.