Targeting ß3-adrenergic receptor signaling inhibits neuroblastoma cell growth via suppressing the mTOR pathway.

ABSTRACT

Neuroblastoma (NB), the most common extracranial solid tumor in childhood, always leads to an unfavorable prognosis. ß3-adrenergic receptor (ß3-AR) signaling plays an important role in lipid metabolism. Although previous studies have focused mainly on the role of ß2-AR in tumor cells; there are few studies about the cancer-related function of ß3-AR. Herein, we showed that ß3-AR expression was significantly increased in clinical NB tissue compared with that in the less malignant ganglioneuroma (GN) and ganglioneuroblastoma (GNB) tissues. Further cellular assays demonstrated that treatment of NB cells with SR59230A (a specific ß3-AR antagonist) suppressed NB cells growth and colony formation, and siRNA knockdown of ß3-AR expression also inhibited NB cell proliferation. The mechanistic study revealed that ß3-AR knockdown and SR59230A inhibited the phosphorylation and thereby the activation of the mTOR/p70S6K pathway. Activation of the mTOR pathway with the activator MHY1485 reversed the inhibitory effect of SR59230A on NB cell growth. Above all, our study clarifies a novel regulatory role of ß3-AR in NB cell growth and provides a potent therapeutic strategy for this disease by specific targeting of the ß3-AR pathway.