Introduction:
Neuroblastoma (NB) is one of the most common extracranial solid malignant
tumors in children. The 5-year survival rate of high-risk or refractory NB is less than 50%. Therefore, developing new effective
therapeutics for NB remains an urgent challenge. Materials and Methods: Based on the NB dataset TARGET-NBL in the TCGA database, the prognosis-related genes were analyzed using univariate cox regression (p < 0.01). The
protein network interaction of prognostic genes was analyzed using STRING to obtain 150 hub genes with HR > 1 and 150 hub genes with HR < 1. The Connectivity Map database was used to predict a therapeutic drug:
BI-D1870, a ribosomal
S6 kinase inhibitor. The inhibitory effect of
BI-D1870 on NB was investigated through in vivo and in vitro experiments, and its inhibitory mechanism was explored. Results: Both the in vivo and in vitro experiments showed that
BI-D1870 could inhibit
tumor proliferation and induce
tumor apoptosis. Furthermore, we proved that
BI-D1870 caused G2/M phase arrest and mitosis damage in cells.
RNA-seq of cells showed that
BI-D1870 may inhibit the growth of NB by inhibiting the PI3K-Akt-mTOR axis. Western blot and immunofluorescence testing showed that
BI-D1870 inhibited the PI3K-Akt-mTORC1 signal pathway to regulate the phosphorylation of RPS6 and 4E BP1
proteins, inhibit protein translation, and inhibit microtubule formation, thus preventing mitotic proliferation and inducing apoptosis. Conclusions: This study provides strong support that
BI-D1870 may be a potential adjuvant
therapy for NB.