Notoginsenoside R7 suppresses cervical cancer via PI3K/PTEN/Akt/mTOR signaling
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Li Li1,3,*, Jin-Xia Sun1,2,*, Xiao-Qi Wang4, Xiao-Kai Liu1,2, Xian-Xiong Chen1,2, Bo Zhang1, Zhen-Dan He1, Dong-Zhou Liu4, Li-Xin Chen5, Li-Wei Wang5 and Zhong Huang1,2
1Institute of Biological Therapy, Shenzhen University, Shenzhen 518060, China
2Department of Immunology, Shenzhen University School of Medicine, Shenzhen 518060, China
3Department of Pharmacy, The Eighth Affiliated Hospital of Zhongshan University, Shenzhen 518000, China
4Department of Rheumatology & Immunology, Ji’nan University 2nd Clinical Medicine College, Shenzhen People’s Hospital, Shenzhen 518020, China
5Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China
*These authors have contributed equally to this work
Zhong Huang, email: [email protected]
Keywords: notoginsenoside R7; PI3K/PTEN/Akt/mTOR; apoptosis; proliferation; cervix cancer
Received: May 25, 2017 Accepted: August 04, 2017 Published: November 27, 2017
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.
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