Abstract
Glioblastoma (GBM) is one of the most malignant forms of intracranial tumors, with high mortality rates and invariably poor prognosis, due to the limited clinical treatment strategies available. As a natural compound, peimine's favorable pharmacological activities have been widely revealed. However, potential inhibitory effects of peimine on GBM have not been explored. In the present study, both in vitro and in vivo experiments were performed to elucidate the effects of peimine on GBM and to further delineate the underlying molecular mechanism of action. Different doses (0, 25 and 50 µM) of peimine were added to U87 cells, before MTT, colony formation, wound healing, Transwell migration and invasion, reactive oxygen species and mitochondrial transmembrane potential assays were used to measure proliferation, migration, invasion and apoptosis. Furthermore, western blotting was used to examine the possible effects of peimine on the expression of proteins associated with apoptosis and the PI3K/AKT signaling pathway. Subsequently, a GBM mouse xenograft model was used to assess the effects of peimine in vivo. The findings showed that peimine inhibited GBM proliferation, migration and invasion in a dose-dependent manner, whilst also inducing apoptosis. Peimine also reduced tumor growth in vivo. Mechanistically, peimine downregulated the expression of Bcl-2 and Caspase 3, whilst upregulating the protein expression levels of p53, Bax and Cleaved-Caspase 3 in a dose-dependent manner. In addition, PI3K and AKT phosphorylation levels were found to be decreased by peimine in a dose-dependent manner. In conclusion, these findings suggest that peimine may limit GBM growth by regulating the PI3K/AKT signaling pathway both in vitro and in vivo. These findings may have promising clinical implications.