A network pharmacology- and transcriptomics-based investigation reveals an inhibitory role of β-sitosterol in glioma via the EGFR/MAPK signaling pathway

Glioma is characterized by rapid cell proliferation, aggressive invasion, altered apoptosis and a poor prognosis. beta-Sitosterol, a kind of phytosterol, has been shown to possess anticancer activities. Our current study aims to investigate the effects of beta-sitosterol on gliomas and reveal the underlying mechanisms. Our results show that beta-sitosterol effectively inhibits the growth of U87 cells by inhibiting proliferation and inducing G2/M phase arrest and apoptosis. In addition, beta-sitosterol inhibits migration by downregulating markers of epithelial-mesenchymal transition (EMT). Mechanistically, network pharmacology and transcriptomics approaches illustrate that the EGFR/MAPK signaling pathway may be responsible for the inhibitory effect of beta-sitosterol on glioma. Afterward, the results show that beta-sitosterol effectively suppresses the EGFR/MAPK signaling pathway. Moreover, beta-sitosterol significantly inhibits tumor growth in a U87 xenograft nude mouse model. beta-Sitosterol inhibits U87 cell proliferation and migration and induces apoptosis and cell cycle arrest in U87 cells by blocking the EGFR/MAPK signaling pathway. These results suggest that beta-sitosterol may be a promising therapeutic agent for the treatment of glioma.