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

doi:10.1177/1535370214554881

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells
	Huang, Ou 3; Zhang, Weili 4; Zhi, Qiaoming 1; Xue, Xiaofeng 1; Liu, Hongchun2 ; Shen, Daoming 4; Geng, Meiyu2 ; Xie, Zuoquan2 ; Jiang, Min 1
刊名	EXPERIMENTAL BIOLOGY AND MEDICINE
	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
DOI	10.1177/1535370214554881
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.
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
WOS研究方向	Research & Experimental Medicine
语种	英语
出版者	SAGE PUBLICATIONS LTD
WOS记录号	WOS:000353054600003
内容类型	期刊论文
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.