Modeling the mitotic regulatory network identifies highly efficient   anti-cancer drug combinations

doi:10.1039/c4mb00610k

CORC > 北京大学 > 化学与分子工程学院

	Modeling the mitotic regulatory network identifies highly efficient anti-cancer drug combinations
	Wu, Yiran ; Zhuo, Xiaolong ; Dai, Ziwei ; Guo, Xiao ; Wang, Yao ; Zhang, Chuanmao ; Lai, Luhua
刊名	分子生物系统
	2015
关键词	SPINDLE-ASSEMBLY CHECKPOINT CELL-CYCLE OSCILLATOR AURORA-A KINASE UBIQUITIN-CONJUGATING ENZYME POLO-LIKE KINASES IN-SILICO TARGETING MITOSIS SYSTEMS BIOLOGY B KINASE CANCER
DOI	10.1039/c4mb00610k
英文摘要	Targeting mitotic regulation is recognized as an important strategy for cancer therapy. Aurora A/B kinase and polo-like kinase 1 (PLK1) are the key mitotic regulators, and many inhibitors have been developed. Combinations of these inhibitors are anticipated to be more effective therapeutics compared with single-inhibitor treatments; however, a systematic analysis of the combined effects is lacking. Here, we constructed the first mammalian cell mitotic regulation network model, which spans from mitotic entry to anaphase initiation, and contains all key mitotic kinase targets. The combined effects of different kinase inhibitors and microtubule inhibitors were systematically explored. Simultaneous inhibition of Aurora B and PLK1 strongly induces polyploidy. Microtubule inhibitor dosage can be significantly reduced when combined with a PLK1 inhibitor. The efficacy of these inhibitor combinations was validated by our experimental results. The mitotic regulatory network model provides a platform to study the complex interactions during mitosis, enables identification of mitotic regulators, and determines targets for drug discovery research. The suggested use of combining microtubule inhibitors with PLK1 inhibitors is anticipated to enhance microtubule-inhibitor tolerance in a wide range of patients.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000348211900017&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Biochemistry & Molecular Biology; SCI(E); PubMed; 0; ARTICLE; zhangcm@pku.edu.cn; lhlai@pku.edu.cn; 2; 497-505; 11
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/149648]
专题	化学与分子工程学院生命科学学院
推荐引用方式 GB/T 7714	Wu, Yiran,Zhuo, Xiaolong,Dai, Ziwei,et al. Modeling the mitotic regulatory network identifies highly efficient anti-cancer drug combinations[J]. 分子生物系统,2015.
APA	Wu, Yiran.,Zhuo, Xiaolong.,Dai, Ziwei.,Guo, Xiao.,Wang, Yao.,...&Lai, Luhua.(2015).Modeling the mitotic regulatory network identifies highly efficient anti-cancer drug combinations.分子生物系统.
MLA	Wu, Yiran,et al."Modeling the mitotic regulatory network identifies highly efficient anti-cancer drug combinations".分子生物系统 (2015).