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学科主题: 基础医学
题名:
Curcumin inhibits tumor proliferation induced by neutrophil elastase through the upregulation of alpha 1-antitrypsin in lung cancer
作者: Xu, Yan1,2; Zhang, Jingjie1,2; Han, Jing1,2; Pan, Xueyang1,2; Cao, Yajun1,2,3; Guo, Hao1,2; Pan, Yan1,2; An, Yu1,2; Li, Xuejun1,2
关键词: Curcumin ; Tumor proliferation ; alpha 1-antitrypsin ; Neutrophil elastase
刊名: MOLECULAR ONCOLOGY
发表日期: 2012-08-01
DOI: 10.1016/j.molonc.2012.03.005
卷: 6, 期:4, 页:405-417
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: FACTOR-KAPPA-B ; NONSMALL CELL LUNG ; PANCREATIC-CANCER ; OVARIAN-CANCER ; ANGIOGENESIS ; APOPTOSIS ; INFLAMMATION ; CARCINOMA ; MECHANISM ; GENE
英文摘要:

Lung carcinogenesis is a complex process in an unregulated inflammatory environment. Curcumin has been extensively investigated as a multi-target anti-tumor and anti-inflammation compound. In this paper, we demonstrate a novel inflammation-related mechanism for curcumin-induced inhibition of lung tumor growth. We found that neutrophil elastase, an important regulator of inflammatory processes, directly triggered tumor cell proliferation in human lung adenocarcinoma A549 cells, and curcumin could completely suppress the excess tumor proliferation induced by neutrophil elastase. alpha 1-antitrypsin is synthesized by tumor cells and is the natural inhibitor of neutrophil elastase. We found that curcumin counteracted the decrease of alpha 1-antitrypsin induced by neutrophil elastase by inducing the promoter activity of alpha 1-antitrypsin and promoting its expression in A549 cells. The inhibition of neutrophil elastase-induced proliferation by curcumin was dependent on the PI3K/Akt pathway. Knockdown of alpha 1-antitrypsin by siRNA further enhanced the tumor cell proliferation induced by neutrophil elastase and significantly blocked the anti-proliferation effect of curcumin against neutrophil elastase. Curcumin remarkably inhibited the primary tumor growth of Lewis lung carcinoma (LLC) in C57BL/6 mice. We further showed that curcumin upregulated the level of alpha 1-antitrypsin in primary tumor tissue by promoting its local expression, and the protein level of neutrophil elastase in tumor tissue was obviously decreased in mice treated with curcumin. Overall, our results suggest that neutrophil elastase and alpha 1-antitrypsin play important roles in modulating lung tumor proliferation in inflammatory microenvironment and curcumin inhibits neutrophil elastase-induced tumor proliferation via upregulating alpha 1-antitrypsin expression in vitro and in vivo. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 81020108031 ; 30572202 ; 30973558 ; 91129727 ; 30901815 ; 30901803 ; 2009ZX09103-144 ; B07001
项目资助者: National Natural Science Foundation of China ; Major Specialized Research Fund from the Ministry of Science and Technology in China ; Research Fund from Ministry of Education of China
WOS记录号: WOS:000307531200003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57432
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.Peking Univ, State Key Lab Nat & Biomimet Drugs, Dept Pharmacol, Sch Basic Med Sci, Beijing 100191, Peoples R China
3.Shihezi Univ, Key Lab Xinjiang Phytomed Resources Modernizat TC, Sch Pharmaceut Sci, Shihezi 832002, Xinjiang, Peoples R China

Recommended Citation:
Xu, Yan,Zhang, Jingjie,Han, Jing,et al. Curcumin inhibits tumor proliferation induced by neutrophil elastase through the upregulation of alpha 1-antitrypsin in lung cancer[J]. MOLECULAR ONCOLOGY,2012,6(4):405-417.
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