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学科主题: 基础医学
题名:
Atorvastatin sensitizes human non-small cell lung carcinomas to carboplatin via suppression of AKT activation and upregulation of TIMP-1
作者: Chen, Jie2,3; Lan, Tian4; Hou, Jincai1; Zhang, Jingjie2,3; An, Yu2,3; Tie, Lu2,3; Pan, Yan2,3; Liu, Jicheng1; Li, Xuejun2,3
关键词: Atorvastatin ; Carboplatin ; AKT ; TIMP-1 ; Lung cancer
刊名: INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
发表日期: 2012-05-01
DOI: 10.1016/j.biocel.2012.01.015
卷: 44, 期:5, 页:759-769
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: COA REDUCTASE INHIBITORS ; OVARIAN-CANCER CELLS ; MATRIX METALLOPROTEINASES-1 ; SYNERGISTIC INHIBITION ; CISPLATIN RESISTANCE ; MAMMALIAN TARGET ; TISSUE INHIBITOR ; KINASE-B ; STATINS ; PATHWAY
英文摘要:

Platinum-based chemotherapy is the standard treatment for advanced non-small-cell lung carcinomas (NSCLCs). However, the antitumoral effect of carboplatin displays unsatisfactory in NSCLCs treatment due to the AKT pathway-mediated carboplatin insensitive in NSCLCs treatment. Previous studies have shown that statins have antitumor activity, but it is unknown whether atorvastatin can reverse carboplatin resistance in lung cancer. Treatment with atorvastatin and carboplatin reduced the growth of xenograft A549 tumors in nude mice and enhanced the survival rate compared with carboplatin alone. Atorvastatin in combination with carboplatin had stronger effects on growth inhibition and apoptosis of NSCLC than either agent used individually. Carboplatin conferred anti-invasive effect in NSCLC cells mainly through inhibition of AKT activity and resultant upregulation of TIMP-1. However, the inhibitory effect on AKT activity by carboplatin was short-term. Additional atorvastatin administration resulted in synergistic inhibition of NSCLC cell invasion and stimulation of TIMP-1 expression with carboplatin through stronger and persistent inhibition of AKT activity both in vivo and in vitro. The synergy of atorvastatin and carboplatin was confirmed using another human lung carcinoma cell line (H1299). Altogether, our data demonstrate that atorvastatin may overcome carboplatin resistance in lung cancer by suppressing AKT activity and upregulating TIMP-1. A combination of atorvastatin and carboplatin may be an effective strategy in clinical therapy against NSCLCs. (c) 2012 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 81020108031 ; 30572202 ; 30973558 ; 30772571 ; 30901815 ; 30901803 ; 30973902 ; 2009ZX09103-144 ; B07001 ; D200929
项目资助者: National Natural Science Foundation of China ; Ministry of Science and Technology in China ; Ministry of Education of China ; Province Natural Science Foundation of Hei Long Jiang
WOS记录号: WOS:000303558600016
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63900
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Peking Univ, Inst Syst Biomed, Beijing 100191, Peoples R China
2.Qi Qi Ha Er Med Univ, Med & Drug Res Inst, Hei Long Jiang 161009, Peoples R China
3.Peking Univ, State Key Lab Nat & Biomimet Drugs, Dept Pharmacol, Sch Basic Med Sci, Beijing 100191, Peoples R China
4.Guangdong Pharmaceut Univ, Vasc Biol Res Inst, Guangzhou 510006, Guangdong, Peoples R China

Recommended Citation:
Chen, Jie,Lan, Tian,Hou, Jincai,et al. Atorvastatin sensitizes human non-small cell lung carcinomas to carboplatin via suppression of AKT activation and upregulation of TIMP-1[J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,2012,44(5):759-769.
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