Thioredxin reductase inhibitor ethaselen increases the drug sensitivity   of the colon cancer cell line LoVo towards cisplatin via regulation of   G1 phase and reversal of G2/M phase arrest

doi:10.1007/s10637-010-9401-y

CORC > 北京大学 > 生命科学学院

	Thioredxin reductase inhibitor ethaselen increases the drug sensitivity of the colon cancer cell line LoVo towards cisplatin via regulation of G1 phase and reversal of G2/M phase arrest
	Fu, Jia-ning ; Li, Jing ; Tan, Qiang ; Yin, Han-wei ; Xiong, Kun ; Wang, Tian-yu ; Ren, Xiao-yuan ; Zeng, Hui-hui
刊名	investigational new drugs
	2011
关键词	Ethaselen Cisplatin Combination index Cell cycle regulation LoVo DNA-DAMAGE QUANTITATIVE-ANALYSIS INDUCED CYTOTOXICITY POSSIBLE INVOLVEMENT CYCLE APOPTOSIS P53 MECHANISM GROWTH UCN-01
DOI	10.1007/s10637-010-9401-y
英文摘要	We evaluated the combination treatment of ethaselen (BBSKE) as a thioredoxin reductase (TrxR) inhibitor plus cisplatin (CDDP) on the human colon adenocarcinoma cell line LoVo. Therapeutic effects ranging from nearly additive to clearly synergistic demonstrated an effective combination, i.e., the cytostatic dose of CDDP could be reduced without a loss in efficacy. To further investigate the cellular response mechanisms of these favorable outcomes, we analyzed the cell-cycle profiles, mRNA expression patterns, and protein levels of several key genes after incubation with BBSKE or CDDP separately and in combination. In appropriate conditions, CDDP induced arrest at the G2/M phase accompanied by the enhanced inhibitory phosphorylation of Cdk1 and the elevated protein expression of cyclin B1. BBSKE downregulated expression of cyclin D1 by increasing mRNA and protein levels of p21, and thus induced G1 phase arrest. BBSKE returned Cdk1 to an activated state, and reduced the protein level of cyclin B1 after incubation in combination with CDDP, which was consistent with the reduction in the percentage of cells in G2/M identified by flow cytometry. By regulating the G1 phase and reversing CDDP-induced G2/M phase arrest, BBSKE increases drug sensitivity of LoVo cells toward CDDP, and probably provides a meaningful anticancer strategy for further clinical studies.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000291061200011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Oncology; Pharmacology & Pharmacy; SCI(E); PubMed; 16; ARTICLE; 4; 627-636; 29
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/156764]
专题	生命科学学院
推荐引用方式 GB/T 7714	Fu, Jia-ning,Li, Jing,Tan, Qiang,et al. Thioredxin reductase inhibitor ethaselen increases the drug sensitivity of the colon cancer cell line LoVo towards cisplatin via regulation of G1 phase and reversal of G2/M phase arrest[J]. investigational new drugs,2011.
APA	Fu, Jia-ning.,Li, Jing.,Tan, Qiang.,Yin, Han-wei.,Xiong, Kun.,...&Zeng, Hui-hui.(2011).Thioredxin reductase inhibitor ethaselen increases the drug sensitivity of the colon cancer cell line LoVo towards cisplatin via regulation of G1 phase and reversal of G2/M phase arrest.investigational new drugs.
MLA	Fu, Jia-ning,et al."Thioredxin reductase inhibitor ethaselen increases the drug sensitivity of the colon cancer cell line LoVo towards cisplatin via regulation of G1 phase and reversal of G2/M phase arrest".investigational new drugs (2011).