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

Xie Yufang; Chen Zhijian; Li Shuang; Yan Meijuan; He Wenjun; Li Li; Si Junqiang; Wang Yan; Li Xinzhi; Ma Ketao

doi:10.3724/abbs.2023251

Acta Biochimica et Biophysica Sinica (Dec 2023)

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

Xie Yufang,
Chen Zhijian,
Li Shuang,
Yan Meijuan,
He Wenjun,
Li Li,
Si Junqiang,
Wang Yan,
Li Xinzhi,
Ma Ketao

Affiliations

Xie Yufang: ["Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi 832000, China","Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832000, China","Department of Physiology, Shihezi University School of Medicine, Shihezi 832000, China"]
Chen Zhijian: ["Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi 832000, China","Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832000, China","Department of Pathophysiology, Shihezi University School of Medicine, Shihezi 832000, China"]
Li Shuang: ["Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi 832000, China","Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832000, China","Department of Pathophysiology, Shihezi University School of Medicine, Shihezi 832000, China"]
Yan Meijuan: ["Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi 832000, China","Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832000, China","Department of Physiology, Shihezi University School of Medicine, Shihezi 832000, China"]
He Wenjun: ["Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi 832000, China","Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832000, China","Department of Physiology, Shihezi University School of Medicine, Shihezi 832000, China"]
Li Li: ["Department of Physiology, Shihezi University School of Medicine, Shihezi 832000, China"]
Si Junqiang: ["Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi 832000, China","Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832000, China","Department of Physiology, Shihezi University School of Medicine, Shihezi 832000, China"]
Wang Yan: ["Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi 832000, China","Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832000, China"]
Li Xinzhi: ["Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi 832000, China","Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832000, China","Department of Pathophysiology, Shihezi University School of Medicine, Shihezi 832000, China"]
Ma Ketao: ["Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi 832000, China","Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832000, China","Department of Physiology, Shihezi University School of Medicine, Shihezi 832000, China"]

DOI: https://doi.org/10.3724/abbs.2023251
Journal volume & issue: Vol. 56
pp. 223 – 238

Abstract

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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 reveal the underlying mechanisms. Our results show that β-sitosterol effectively inhibits the growth of U87 cells by inhibiting proliferation and inducing G2/M phase arrest and apoptosis. In addition, β-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 β-sitosterol on glioma. Afterward, the results show that β-sitosterol effectively suppresses the EGFR/MAPK signaling pathway. Moreover, β-sitosterol significantly inhibits tumor growth in a U87 xenograft nude mouse model. β-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 β-sitosterol may be a promising therapeutic agent for the treatment of glioma.

Published in Acta Biochimica et Biophysica Sinica

ISSN: 1672-9145 (Print); 1745-7270 (Online)
Publisher: China Science Publishing & Media Ltd.
Country of publisher: China
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry; Science: Biology (General): Genetics
Website: https://www.sciengine.com/ABBS/home

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