Study of mechanism of action of specific inhibitor of COX-2 on Egr-1

JIANG Bing; et al

doi:10.13406/j.cnki.cyxb.2010.12.022

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Study of mechanism of action of specific inhibitor of COX-2 on Egr-1

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- Study of mechanism of action of specific inhibitor of COX-2 on Egr-1
- Journal of Chongqing Medical University Vol. 35, Issue 12, Pages: 1787-1790(2010)
- 作者机构：
  
  1. 重庆医科大学附属永川医院呼吸内科
  2. 重庆医科大学附属第二医院呼吸内科
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.2010.12.022
  CLC： R734.2
- Published：2010，
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[1]江兵,蒋幼凡,秦光梅,李良兰.选择性环氧化酶-2抑制剂调节Egr-1作用机制的研究[J].重庆医科大学学报,2010,35(12):1787-1790.

JIANG Bing, et al. Study of mechanism of action of specific inhibitor of COX-2 on Egr-1. [J]. Journal of Chongqing Medical University 35(12):1787-1790(2010)
[1]江兵,蒋幼凡,秦光梅,李良兰.选择性环氧化酶-2抑制剂调节Egr-1作用机制的研究[J].重庆医科大学学报,2010,35(12):1787-1790. DOI： 10.13406/j.cnki.cyxb.2010.12.022.

JIANG Bing, et al. Study of mechanism of action of specific inhibitor of COX-2 on Egr-1. [J]. Journal of Chongqing Medical University 35(12):1787-1790(2010) DOI： 10.13406/j.cnki.cyxb.2010.12.022.

摘要

目的:以肺腺癌细胞株A549为研究对象

观察不同浓度的塞来昔布对A549细胞的生长周期及凋亡率的影响

以及对早期反应基因-1（Early growth response-1

Egr-1）表达的影响

探讨环氧化酶-2（Cyclooxygenase-2

COX-2）抑制剂调节Egr-1的具体机制

从分子水平上寻找COX-2抑制剂抗肿瘤作用的具体机制

进一步指导临床治疗。方法:体外培养肺腺癌细胞A549

经25.0、50.0、100.0μmol/L浓度的塞来昔布处理细胞

24 h后采用流式细胞仪（Flowcytometer

FCM）测定细胞周期

TUNEL法测定细胞凋亡

RT-PCR法检测Egr-1、Fas基因的表达。结果:25.0、50.0、100.0μmol/L赛来昔布作用24 h后

A549细胞不同程度的阻滞在G0/G1期

A549细胞凋亡指数分别是10.67%±1.46%、18.33%±2.54%、25.67%±2.10%

差异具有统计学意义（P<0.05）;随着塞来昔布药物浓度的增加

Egr-1和Fas的mRNA表达量逐步增加

差异具有统计学意义（P<0.05）。结论:高度选择性COX-2抑制剂塞来昔布可通过调节细胞周期和细胞凋亡发挥抗肿瘤作用

其作用机制可能是通过上调细胞中Egr-1的表达

进而上调Fas的表达

使细胞周期阻滞于G0/G1

最终促进细胞凋亡

这可能是环氧化酶抑制剂发挥抗癌作用的分子生物学基础。

Abstract

Objective:To study the effects of specific inhibitor of COX-2 celecoxib in different concentration on cell apoptosis

cell cycle and expression of Egr-1 of A549 cells

and to investigate the molecular mechanism of anti-tumor effects.Methods:A549 cells were cultured in vitro and treated by 25.0

50.0 μmol/L and 100.0 μmol/L celecoxib.Then the TUNEL assay was used to detect apoptosis;FCM assay was used to determine cell cycle

and RT-PCR assay was performed to evaluate the Egr-1 and Fas mRNA expression levels.Results:Treated by celecoxib in the concentration of 25.0

50.0 μmol/L and 100.0 μmol/L

the cell cycle was arrested in c phase in A549 cells respectively;the apoptotic index of A549 cells were 10.67%±1.46%

18.83%±2.54% and 25.67%±2.10% respectively

and the expression levels of Egr-1 and Fas mRNA were up-regulated synchronously.Conclusion:Celecoxib

a specific inhibitor of COX-2

can inhibit the proliferation of A549 cells by regulating the cell cycle and inducing the cell apoptosis.The molecular mechanism may be that COX-2 inhibitor up-regulates the expression of Fas by up-regulating the expression of Egr-1

and then induces the cell apoptosis by blocking the A549 cells in G0/G1 period.

关键词

环氧化酶-2抑制剂肺癌早期反应基因-1

Keywords

Cyclooxygenase-2lung cancerEarly growth response-1

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