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Targeting AKT with Oridonin Inhibits Growth of Esophageal Squamous Cell Carcinoma In Vitro and Patient-Derived Xenografts In Vivo

文献类型：期刊论文

作者Song, Mengqiu2,3; Liu, Xuejiao3; Liu, Kangdong2,3,4; Zhao, Ran2,3; Huang, Hai3; Shi, Yuanyuan3; Zhang, Man3; Zhou, Silei3; Xie, Hua5; Chen, Hanyong6
刊名MOLECULAR CANCER THERAPEUTICS
出版日期2018-07
卷号17期号:7页码:1540-1553
ISSN号1535-7163
DOI10.1158/1535-7163.MCT-17-0823
文献子类Article
英文摘要Overexpression or activation of AKT is very well known to control cell growth, survival, and gene expression in solid tumors. Oridonin, an inflammatory medical and diterpenoid compound isolated from Rabdosia rubescens, has exhibited various pharmacologic and physiologic properties, including antitumor, antibacterial, and anti-inflammatory effects. In this study, we demonstrated that oridonin is an inhibitor of AKT and suppresses proliferation of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. The role of AKT in ESCC was studied using immuno-histochemical analysis of a tumor microarray, the effect of AKT knockdown on cell growth, and treatment of cells with MK-2206, an AKT inhibitor. Oridonin blocked AKT kinase activity and interacted with the ATP-binding pocket of AKT. It inhibited growth of KYSE70, KYSE410, and KYSE450 esophageal cancer cells in a time- and concentration-dependent manner. Oridonin induced arrest of cells in the G2-M cell-cycle phase, stimulated apoptosis, and increased expression of apoptotic biomarkers, including cleaved PARP, caspase-3, caspase-7, and Bims in ESCC cell lines. Mechanistically, we found that oridonin diminished the phosphorylation and activation of AKT signaling. Furthermore, a combination of oridonin and 5-fluorouracil or cisplatin (clinical chemotherapeutic agents) enhanced the inhibition of ESCC cell growth. The effects of oridonin were verified in patient-derived xenograft tumors expressing high levels of AKT. In summary, our results indicate that oridonin acts as an AKT inhibitor to suppress the growth of ESCC by attenuating AKT signaling. Mol Cancer Ther; 17(7); 1540-53. (C) 2018 AACR.
WOS关键词LUNG-CANCER CELLS ; PI3K/AKT PATHWAY ; RABDOSIA-RUBESCENS ; INDUCED APOPTOSIS ; AUTOPHAGY ; PROLIFERATION ; MALIGNANCIES ; ACTIVATION ; DESIGN ; MODELS
资助项目NIH, USA[CA187027] ; NIH, USA[CA 166011] ; NIH, USA[CA 196639] ; Key program of Henan Province, China[161100510300] ; National Natural Science Foundation of China[NSFC81672767] ; National Natural Science Foundation of China[NSFC81372269] ; National Natural Science Foundation of China[NSFC81572812] ; Henan Provincial Government, China[00000000]
WOS研究方向Oncology
语种英语
WOS记录号WOS:000437274600017
出版者AMER ASSOC CANCER RESEARCH
源URL[http://119.78.100.183/handle/2S10ELR8/279685]  
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Dong, Zigang; Lee, Mee-Hyun
作者单位1.Zhengzhou Univ, Henan Canc Hosp, Dept Thorac Surg, Affiliated Canc Hosp, Zhengzhou, Henan, Peoples R China;
2.Zhengzhou Univ, Sch Basic Med Sci, Dept Pathophysiol, Zhengzhou, Henan, Peoples R China;
3.China US Henan Hormel Canc Inst, 127 Dongming Rd, Zhengzhou 450008, Henan, Peoples R China;
4.Collaborat Innovat Ctr Henan Prov Canc Chemopreve, Zhengzhou, Henan, Peoples R China;
5.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai, Peoples R China;
6.Univ Minnesota, Hormel Inst, 801 16th Ave NE, Austin, MN 55912 USA;
7.Shantou Univ, Dept Biochem & Mol Biol, Med Coll, Shantou, Guangdong, Peoples R China
推荐引用方式
GB/T 7714		 Song, Mengqiu,Liu, Xuejiao,Liu, Kangdong,et al. Targeting AKT with Oridonin Inhibits Growth of Esophageal Squamous Cell Carcinoma In Vitro and Patient-Derived Xenografts In Vivo[J]. MOLECULAR CANCER THERAPEUTICS,2018,17(7):1540-1553.
APA Song, Mengqiu.,Liu, Xuejiao.,Liu, Kangdong.,Zhao, Ran.,Huang, Hai.,...&Lee, Mee-Hyun.(2018).Targeting AKT with Oridonin Inhibits Growth of Esophageal Squamous Cell Carcinoma In Vitro and Patient-Derived Xenografts In Vivo.MOLECULAR CANCER THERAPEUTICS,17(7),1540-1553.
MLA Song, Mengqiu,et al."Targeting AKT with Oridonin Inhibits Growth of Esophageal Squamous Cell Carcinoma In Vitro and Patient-Derived Xenografts In Vivo".MOLECULAR CANCER THERAPEUTICS 17.7(2018):1540-1553.

入库方式： OAI收割

来源：上海药物研究所

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