PI3K/AKT/mTOR通路
蛋白激酶B
癌症研究
化学
自噬
细胞凋亡
药理学
细胞生长
RPTOR公司
细胞生物学
mTORC1型
信号转导
体内
MAPK/ERK通路
癌细胞
下调和上调
活力测定
作者
Pei-Li Zhu,Dick Fai Lam,Jun-Kui Li,Xiu-Qiong Fu,Cheng-Le Yin,Ji-Yao Chou,Ya-Ping Wang,Yu-Xi Liu,Ying-Jie Chen,Jia-Ying Wu,Ying Wu,Jing-Xuan Bai,Chun Liang,Zhi-Ling Yu
标识
DOI:10.1248/bpb.b20-00030
摘要
Primary liver cancer is a lethal cancer. The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway has been implicated in the pathogenesis of liver cancer. Gomisin N (GN), a lignan isolated from the dried fruits of Schisandra chinensis (Turca.) Baill., has been reported to reduce viability of, and induce apoptosis in, HepG2 liver cancer cells. In preadipocytes, GN was found to inhibit Akt activity. In the present study, Akt signaling-related anti-liver cancer mechanisms of GN were investigated. We confirmed that GN reduces cell viability of, and triggers apoptosis in, more liver cancer cell lines. Mechanistic studies revealed that GN lowers protein levels of phospho-PI3K (p85 tyrosine (Tyr)458), phospho-Akt (serine (Ser)473), and Akt downstream molecules Mcl-1 in HepG2 and HCCLM3 cells. Meanwhile, GN activates mTOR and inhibits ULK1 (a negative downstream effector of mTOR) activities. Activation of mTOR has been reported to suppress ULK1 activity and repress autophagy. Indeed, we observed that GN inhibits autophagy in liver cancer cells. In summary, we for the first time demonstrated that GN inhibits the PI3K-Akt pathway and regulates the mTOR-ULK1 pathway in liver cancer cells.
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