PI3K/AKT/mTOR通路
蛋白激酶B
细胞凋亡
癌症研究
体内
信号转导
细胞生长
体外
药理学
化学
细胞生物学
生物
生物化学
遗传学
作者
Jianhong Dong,Yong Qian,Wei Zhang,Jiayun Xu,Li-pei Wang,Ziwei Fan,Mengxian Jia,Lijia Wei,Hui Yang,Xuan Luo,Yongjie Wang,Yuanyuan Jiang,Zhihui Huang,Ying Wang
标识
DOI:10.1016/j.ejphar.2024.176401
摘要
Glioblastoma (GBM) is one of the most common intracranial primary malignancies with the highest mortality rate, and there is a lack of effective treatments. In this study, we examined the anti-GBM activity of Tenacissoside H (TH), an active component isolated from the traditional Chinese medicine Marsdenia tenacissima (Roxb.) Wight & Arn (MT), and investigated the potential mechanism. Firstly, we found that TH decreased the viability of GBM cells by inducing cell cycle arrest and apoptosis, and inhibited the migration of GBM cells. Furthermore, combined with the Gene Expression Omnibus database (GEO) and network pharmacology as well as molecular docking, TH was shown to inhibit GBM progression by directly regulating the PI3K/Akt/mTOR pathway, which was further validated in vitro. In addition, the selective PI3K agonist 740 y-p partially restored the inhibitory effects of TH on GBM cells. Finally, TH inhibited GBM progression in an orthotopic transplantation model by inactivating the PI3K/Akt/mTOR pathway in vivo. Conclusively, our results suggest that TH represses GBM progression by inhibiting the PI3K/Akt/mTOR signaling pathway in vitro and in vivo, and provides new insight for the treatment of GBM patients.
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