Aspirin disrupts the mTOR-Raptor complex and potentiates the anti-cancer activities of sorafenib via mTORC1 inhibition
文献类型：期刊论文
| 作者 | Sun, Danni; Liu, Hongchun ; Dai, Xiaoyang; Zheng, Xingling; Yan, Juan; Wei, Rongrui; Fu, Xuhong; Huang, Min; Shen, Aijun; Huang, Xun
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| 刊名 | CANCER LETTERS
 |
| 出版日期 | 2017-10-10 |
| 卷号 | 406页码:105-115 |
| 关键词 | Aspirin mTORC1 AMPK Sorafenib Proliferation |
| ISSN号 | 0304-3835 |
| DOI | 10.1016/j.canlet.2017.06.029 |
| 文献子类 | Article |
| 英文摘要 | Aspirin is associated with a reduced risk of cancer and delayed progression of malignant disease. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mTOR signaling is believed to partially contribute to these anticancer effects, although the mechanism is unclear. In this study, we revealed the mechanism underlying the effects of aspirin on AMPK-mTOR signaling, and described a mechanism-based rationale for the use of aspirin in cancer therapy. We found that aspirin inhibited mTORC1 signaling through AMPK-dependent and-independent manners. Aspirin inhibited the AMPK-TSC pathway, thus resulting in the suppression of mTORC1 activity. In parallel, it directly disrupted the mTOR-raptor interaction. Additionally, the combination of aspirin and sorafenib showed synergetic effects via inhibiting mTORC1 signaling and the PI3K/AKT, MAPK/ERK pathways. Aspirin and sorafenib showed synergetic anticancer efficacy in the SMMC-7721 model. Our study provides mechanistic insights and a mechanism-based rationale for the roles of aspirin in cancer treatment. (C) 2017 Elsevier B.V. All rights reserved. |
| WOS关键词 | ACTIVATED PROTEIN-KINASE ; HISTONE DEACETYLASE INHIBITORS ; BRAF-MUTATION STATUS ; COLORECTAL-CANCER ; CELL-GROWTH ; HEPATOCELLULAR-CARCINOMA ; MAMMALIAN TARGET ; RAPAMYCIN ; COMBINATION ; PATHWAY |
| 资助项目 | Chinese Academy of Sciences[XDA12020000] ; Chinese Academy of Sciences[XDA12020326] ; NSFC-Shandong Joint Fund for Marine Science Research Centers[U1406402] ; Natural Science Foundation of China[81302791] ; Youth Innovation Promotion Association CAS[201663] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000412265000012 |
| 出版者 | ELSEVIER IRELAND LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272455]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Huang, Xun; Ding, Jian; Geng, Meiyu |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sun, Danni,Liu, Hongchun,Dai, Xiaoyang,et al. Aspirin disrupts the mTOR-Raptor complex and potentiates the anti-cancer activities of sorafenib via mTORC1 inhibition[J]. CANCER LETTERS,2017,406:105-115. |
| APA | Sun, Danni.,Liu, Hongchun.,Dai, Xiaoyang.,Zheng, Xingling.,Yan, Juan.,...&Geng, Meiyu.(2017).Aspirin disrupts the mTOR-Raptor complex and potentiates the anti-cancer activities of sorafenib via mTORC1 inhibition.CANCER LETTERS,406,105-115. |
| MLA | Sun, Danni,et al."Aspirin disrupts the mTOR-Raptor complex and potentiates the anti-cancer activities of sorafenib via mTORC1 inhibition".CANCER LETTERS 406(2017):105-115. |
入库方式： OAI收割
来源：上海药物研究所
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