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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-ning1,2; Li, Jing1,2; Tan, Qiang1,3; Yin, Han-wei4; Xiong, Kun4; Wang, Tian-yu4; Ren, Xiao-yuan1,2; Zeng, Hui-hui1,2
关键词Ethaselen Cisplatin Combination index Cell cycle regulation LoVo
刊名INVESTIGATIONAL NEW DRUGS
2011-08-01
DOI10.1007/s10637-010-9401-y
29期:4页:627-636
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology ; Pharmacology & Pharmacy
研究领域[WOS]Oncology ; Pharmacology & Pharmacy
关键词[WOS]DNA-DAMAGE ; QUANTITATIVE-ANALYSIS ; INDUCED CYTOTOXICITY ; POSSIBLE INVOLVEMENT ; CYCLE ; APOPTOSIS ; P53 ; MECHANISM ; GROWTH ; UCN-01
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.

语种英语
WOS记录号WOS:000291061200011
项目编号30472036
资助机构Natural Science Foundation of China
引用统计
被引频次:17[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/68053
专题北京大学药学院
北京大学第一临床医学院_泌尿外科
作者单位1.Peking Univ, Coll Life Sci, Beijing 100075, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
3.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
4.Peking Univ, Hosp 1, Beijing 100034, Peoples R China
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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,2011,29(4):627-636.
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,29(4),627-636.
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 29.4(2011):627-636.
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