A771726, an anti-inflammatory drug, exerts an anticancer effect and reverses tamoxifen resistance in endocrine-resistant breast cancer cells

doi:10.3892/or.2014.3249

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

	A771726, an anti-inflammatory drug, exerts an anticancer effect and reverses tamoxifen resistance in endocrine-resistant breast cancer cells
	Huang, Ou 2; Xie, Zuoquan3 ; Zhang, Weili 4; Lou, Ying 2; Mao, Yan 2; Liu, Hongchun3 ; Jiang, Min 1; Shen, Kunwei 2
刊名	ONCOLOGY REPORTS
	2014-08-05
卷号	32 期号:2 页码:627-634
关键词	A771726 endocrine resistance tamoxifen apoptosis cell cycle microarray analysis
ISSN号	1021-335X
DOI	10.3892/or.2014.3249
文献子类	Article
英文摘要	A771726, an orally available anti-inflammatory agent, has been approved for the treatment of multiple sclerosis by diminishing entire inflammatory responses through multiple signaling pathways. Recently, a few emerging studies have focused on the potential application of A771726 in cancer therapy, less on the treatment of breast cancer and particularly on overcoming drug resistance in breast cancer. We report here for the first time the cytotoxic activity and drug resistance reversal of A771726 in acquired tamoxifen-resistant breast cancer cell line MCF-7/LCC9. We discovered that A771726 treatment showed antiproliferative activities in MCF-7/LCC9 cells, which were even more sensitive to A771726 than their parental tamoxifen-sensitive cells (MCF-7). A771726 also exerted pro-apoptotic activities and induced cell cycle arrest at the G1 phase. Notably, treatment of A771726 restored the sensitivity of MCF-7/LCC9 cells to tamoxifen. Western blot analysis revealed that A771726 decreased the phosphorylation level of Src, one key driver of tamoxifen resistance. Moreover, in order to comprehensively clarify the mechanisms of A771726 in anti-estrogen-resistant cells, we explored a genome-wide transcriptomic analysis, and showed that A771726 could modulate multiple signaling pathways (e.g. cell cycle, apoptosis, MAPK, metabolism and p53 signaling pathway) and cellular processes (e.g. signal transduction, transcription and cell cycle). Overall, our results indicate that A771726 alone and the combination of A771726 with antiestrogens may be of therapeutic benefit for ER-positive and endocrine-resistant breast cancer.
资助项目	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] ; National Science and Technology Major Project of the Ministry of Science and Technology of China[2012ZX09301001-007] ; Leading Academic Discipline Project of Shanghai Municipal Education Commission[J50208] ; Cancer Foundation of China[0901] ; Science and Technology Commission of Shanghai Municipality[09411961400] ; Shanghai Charity Cancer Research Centre[00000000]
WOS关键词	MULTIPLE-SCLEROSIS ; ESTROGEN-RECEPTOR ; ANTIESTROGEN RESISTANCE ; MITOCHONDRIAL-FUNCTION ; CLL CELLS ; TERIFLUNOMIDE ; APOPTOSIS ; SENSITIVITY ; THERAPY ; TRIALS
WOS研究方向	Oncology
语种	英语
出版者	SPANDIDOS PUBL LTD
WOS记录号	WOS:000338908700023
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276949]
专题	药理学第一研究室
通讯作者	Shen, Kunwei
作者单位	1.Soochow Univ, Affiliated Hosp 1, Dept Breast Surg, Suzhou 215006, Jiangsu, Peoples R China 2.Shanghai Jiao Tong Univ, Comprehens Breast Hlth Ctr, Ruijin Hosp, Sch Med, Shanghai 200025, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; 4.Xiangcheng Peoples Hosp, Dept Gastroenterol, Suzhou 215131, Jiangsu, Peoples R China;
推荐引用方式 GB/T 7714	Huang, Ou,Xie, Zuoquan,Zhang, Weili,et al. A771726, an anti-inflammatory drug, exerts an anticancer effect and reverses tamoxifen resistance in endocrine-resistant breast cancer cells[J]. ONCOLOGY REPORTS,2014,32(2):627-634.
APA	Huang, Ou.,Xie, Zuoquan.,Zhang, Weili.,Lou, Ying.,Mao, Yan.,...&Shen, Kunwei.(2014).A771726, an anti-inflammatory drug, exerts an anticancer effect and reverses tamoxifen resistance in endocrine-resistant breast cancer cells.ONCOLOGY REPORTS,32(2),627-634.
MLA	Huang, Ou,et al."A771726, an anti-inflammatory drug, exerts an anticancer effect and reverses tamoxifen resistance in endocrine-resistant breast cancer cells".ONCOLOGY REPORTS 32.2(2014):627-634.