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Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells

文献类型：期刊论文

作者Huang, Ou3; Zhang, Weili4; Zhi, Qiaoming1; Xue, Xiaofeng1; Liu, Hongchun2; Shen, Daoming4; Geng, Meiyu2; Xie, Zuoquan2; Jiang, Min1
刊名EXPERIMENTAL BIOLOGY AND MEDICINE
出版日期2015-04
卷号240期号:4页码:426-437
关键词Triple negative breast cancer teriflunomide growth factor receptor epithelial-mesenchymal transition Src cell cycle
ISSN号1535-3702
DOI10.1177/1535370214554881
文献子类Article
英文摘要Triple-negative breast cancer (TNBC) is defined as a group of primary breast cancers lacking expression of estrogen, progesterone, and human epidermal growth factor receptor-2 (HER-2) receptors, characterized by higher relapse rate and lower survival compared with other subtypes. Due to lack of identified targets and molecular heterogeneity, conventional chemotherapy is the only available option for treatment of TNBC, but non-discordant positive therapeutic efficacy could not be achieved. Here, we demonstrated that these TNBC cells were sensitive to teriflunomide, which was a well-known immunomodulatory drug for treatment of relapsing multiple sclerosis (MS). Potent anti-cancer effects in TNBC in vitro, including proliferation inhibition, cell cycle delay, cell apoptosis, and suppression of cell motility and invasiveness, could be achieved with this agent. Of note, we showed that multiple signals involved in TNBC proliferation, survival, migratory, and invasive potential were under regulation by teriflunomide. Among them, we identified down-regulation of growth factor receptors to abolish growth maintenance, suppression of c-Myc, and cyclin D1 to contribute to its anti-proliferative effect, modulation of components of cell cycle to induce S-phase arrest, degradation of Bcl-xL, and up-regulation of BAX via activation of MAPK pathway to induce apoptosis, and inhibition of epithelial-mesenchymal transition (EMT) process, matrix metalloproteinase-9 (MMP9) expression, and inactivation of Src/FAK to reduce TNBC migration and invasion. The results identified teriflunomide may be of therapeutic benefit for the more aggressive and difficult-to-treat breast cancer subtype, indicating the use of teriflunomide for clinical trials for treatment of TNBC patients.
WOS关键词GROWTH-FACTOR RECEPTOR ; S-PHASE ARREST ; THERAPEUTIC TARGETS ; MOLECULAR PORTRAITS ; MULTIPLE-SCLEROSIS ; SIGNALING PATHWAY ; BASAL-LIKE ; CLL CELLS ; CYCLIN D1 ; IN-VITRO
资助项目National Natural Science Foundation of China[81402176] ; National Natural Science Foundation of China[81202549] ; National Natural Science Foundation of China[81202088] ; National Natural Science Foundation of China[81302147] ; National Natural Science Foundation of China[81302145] ; Natural Science Foundation of Jiangsu Province, China[BK20130270] ; Natural Science Foundation of Jiangsu Province, China[BK20140288] ; Natural Science Foundation of Jiangsu Higher Education Institutions of China[14KJB320011] ; National Science and Technology Major Project of the Ministry of Science and Technology of China[2012ZX09301001-007]
WOS研究方向Research & Experimental Medicine
语种英语
WOS记录号WOS:000353054600003
出版者SAGE PUBLICATIONS LTD
源URL[http://119.78.100.183/handle/2S10ELR8/276583]  
专题药理学第一研究室
通讯作者Jiang, Min
作者单位1.Soochow Univ, Affiliated Hosp 1, Dept Breast Surg, Suzhou 215006, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
3.Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Comprehens Breast Hlth Ctr, Shanghai 200025, Peoples R China;
4.Xiangcheng Peoples Hosp, Dept Gastroenterol, Suzhou 215131, Peoples R China;
推荐引用方式
GB/T 7714		 Huang, Ou,Zhang, Weili,Zhi, Qiaoming,et al. Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells[J]. EXPERIMENTAL BIOLOGY AND MEDICINE,2015,240(4):426-437.
APA Huang, Ou.,Zhang, Weili.,Zhi, Qiaoming.,Xue, Xiaofeng.,Liu, Hongchun.,...&Jiang, Min.(2015).Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells.EXPERIMENTAL BIOLOGY AND MEDICINE,240(4),426-437.
MLA Huang, Ou,et al."Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells".EXPERIMENTAL BIOLOGY AND MEDICINE 240.4(2015):426-437.

入库方式： OAI收割

来源：上海药物研究所

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