Notoginsenoside R7 suppresses cervical cancer via PI3K/PTEN/Akt/mTOR signaling

作者:Li, Li; Sun, Jin-Xia; Wang, Xiao-Qi; Liu, Xiao-Kai; Chen, Xian-Xiong; Zhang, Bo; He, Zhen-Dan; Liu, Dong-Zhou; Chen, Li-Xin; Wang, Li-Wei; Huang, Zhong*
来源:Oncotarget, 2017, 8(65): 109487-109496.
DOI:10.18632/oncotarget.22721

摘要

Notoginsenoside R7 was isolated from Panax notoginseng, a plant used commonly in traditional Chinese medicine. We investigated the anti-cancer effects of R7 in HeLa cells in vitro and in vivo, and explored the underlying mechanisms of action. R7 dose-dependently inhibited HeLa cell proliferation and induced apoptosis in vitro, In silico docking-based screening assays showed that R7 can directly bind Akt. Pretreatment with the Akt inhibitor LY294002 synergistically enhanced the R7 anti-proliferation and anti-apoptosis effects in HeLa cells, confirming that R7 acts through the PI3K/Akt pathway. Consistent with the in vitro findings, R7 exerted anti-tumor effects in a mouse xenograft model by targeting PI3K (PTEN) and Akt, activating the pro-apoptotic Bcl-2 family and, subsequently, caspase family members. R7 treatment activated PTEN and downregulated mTOR phosphorylation without affecting mTOR expression, though regulatory-associated protein of mTOR (raptor) expression declined. Our study suggests that R7 is a promising chemotherapeutic agent for the treatment of cervical cancer and other PI3K/PTEN/Akt/mTOR signaling-associated tumors.