A network pharmacology- and transcriptomics-based investigation reveals an inhibitory role of β-sitosterol in glioma via the EGFR/MAPK signaling pathway
Yufang Xie, Zhijian Chen, Shuang Li, Meijuan Yan, Wen-Jun He, Li Li, Jun‐Qiang Si, Yan Wang, Xinzhi Li, Ketao Ma
Abstract
<p indent="0mm">Glioma is characterized by rapid cell proliferation, aggressive invasion, altered apoptosis and a poor prognosis. β-Sitosterol, a kind of phytosterol, has been shown to possess anticancer activities. Our current study aims to investigate the effects of β-sitosterol on gliomas and try to reveal the underlying mechanisms. Our results showed that β-sitosterol effectively inhibited the growth of U87 cells by inhibiting proliferation and inducing G2/M phase arrest and apoptosis. In addition, β-sitosterol inhibited migration by downregulating markers of epithelial-mesenchymal transition (EMT). Mechanistically, network pharmacology and transcriptomics approaches illustrated that the EGFR/MAPK signaling pathway may be responsible for the inhibitory effect of β-sitosterol on glioma. Afterward, the results showed that β-sitosterol effectively suppressed the EGFR/MAPK signaling pathway. Moreover, β-sitosterol significantly inhibited tumor growth in a U87 xenograft nude model. β-Sitosterol inhibited U87 cell proliferation and migration and induced apoptosis and cell cycle arrest in U87 cells by blocking the EGFR/MAPK signaling pathway. These results provide new insight that β-sitosterol might be a promising therapeutic agent for the treatment of glioma.