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三七皂苷R7通过PI3K/PTEN/Akt/mTOR信号通路抑制宫颈癌。

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

作者信息

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

机构信息

Institute of Biological Therapy, Shenzhen University, Shenzhen 518060, China.

Department of Pharmacy, The Eighth Affiliated Hospital of Zhongshan University, Shenzhen 518000, China.

出版信息

Oncotarget. 2017 Nov 27;8(65):109487-109496. doi: 10.18632/oncotarget.22721. eCollection 2017 Dec 12.

Abstract

Notoginsenoside R7 was isolated from , a plant used commonly in traditional Chinese medicine. We investigated the anti-cancer effects of R7 in HeLa cells and , and explored the underlying mechanisms of action. R7 dose-dependently inhibited HeLa cell proliferation and induced apoptosis , 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 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.

摘要

三七皂苷R7是从一种常用于传统中药的植物中分离得到的。我们研究了R7对HeLa细胞的抗癌作用,并探讨了其潜在的作用机制。R7剂量依赖性地抑制HeLa细胞增殖并诱导凋亡,基于对接的筛选试验表明R7可直接结合Akt。用Akt抑制剂LY294002预处理可协同增强R7对HeLa细胞的抗增殖和抗凋亡作用,证实R7通过PI3K/Akt途径发挥作用。与这些发现一致,R7通过靶向PI3K(PTEN)和Akt,激活促凋亡的Bcl-2家族以及随后的半胱天冬酶家族成员,在小鼠异种移植模型中发挥抗肿瘤作用。R7处理激活了PTEN并下调了mTOR磷酸化,而不影响mTOR表达,尽管mTOR调节相关蛋白(raptor)表达下降。我们的研究表明,R7是一种有前景的化疗药物,可用于治疗宫颈癌和其他与PI3K/PTEN/Akt/mTOR信号相关的肿瘤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c874/5752536/7d906dd897e1/oncotarget-08-109487-g001.jpg

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