吉非替尼联合塞来昔布对肺腺癌细胞凋亡和EGFR、COX2表达的影响

山东大学学报(医学版) ›› 2009, Vol. 47 ›› Issue (8): 37-41.

吉非替尼联合塞来昔布对肺腺癌细胞凋亡和EGFR、COX2表达的影响

王亚丽¹，牟晓燕¹，白小燕¹，马春燕²，范智彦¹

山东大学附属省立医院 1．呼吸科； 2.中心实验室，济南 250021

收稿日期:2008-12-10 发布日期:2009-08-16
通讯作者: 牟晓燕（1966- ），女，副教授，主要从事肺癌发病机制和治疗的研究。 Email: mxy66@126.com
作者简介:王亚丽（1983- ），女，硕士研究生，主要从事肺癌发病机制和治疗的研究。
基金资助:
国家留学归国人员基金项目（2003）。

Effects of Gefitinib in combination with Celecoxib on apoptosis and expressions of EGFR and COX2 in cancerous lung cells

WANG Yali ¹, MU Xiaoyan ¹, BAI Xiaoyan ¹, MA Chunyan ², FAN Zhiyan ¹

1. Department of Respiration； 2. Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China

Received:2008-12-10 Published:2009-08-16

摘要/Abstract

摘要：

目的探讨表皮生长因子受体（EGFR）抑制剂吉非替尼联合环氧合酶2（COX2）抑制剂塞来昔布对肺腺癌A549细胞株凋亡和EGFR、COX2表达的影响。方法A549细胞培养于RPMI1640培养液中,实验分为正常对照组、吉非替尼5?μmol/L组、塞来昔布25?μmol/L组、吉非替尼5?μmol/L联合塞来昔布25?μmol/L组。药物干预细胞48?h后，采用四甲基偶氮唑盐（MTT）比色法测定细胞抑制率、流式细胞术和Hoechst33258染色法检测细胞凋亡和药物作用周期、免疫荧光检测EGFR和COX2蛋白的表达情况。结果吉非替尼和塞来昔布对A549细胞增殖有明显的抑制作用，呈剂量依赖性，两制剂联合作用时抑制作用更强（P<0.01）。吉非替尼和塞来昔布均可诱导细胞凋亡，联合作用后细胞凋亡率更高（P<0.01）；联合用药与单独用药相比，可使细胞发生明显的G1期阻滞（P<0.01），进一步下调了EGFR和COX2蛋白的表达（P<0.05）。结论吉非替尼与塞来昔布联合应用具有协同作用，可进一步抑制细胞的生长。

关键词: 吉非替尼；塞来昔布；细胞凋亡；表皮生长因子受体；环氧合酶2

Abstract:

To explore the effects of Gefitinib in combination with Celecoxib on apoptosis and expressions of EGFR and COX2 in lung cancer A549 cells. MethodsCells were cultured in RPMI1640 and divided into four groups: the control group, the 5?μmol/L Gefitinib group, the 25?μmol/L Celecoxib group, and the 5?μmol/L Gefitinib+25?μmol/L Celecoxib group, which were subjected to drugs for 48 hours. The cell inhibitory rate was detected by methyl thiazolyl tetrazolium(MTT), the apoptotic rate and cell cycle were measured by a flow cytometer and Hoechst33258 staining method, and expressions of EGFR, COX2 were determined by immunofluorescence. ResultsGefitinib and Celecoxib inhibited the growth of A549 cells in a dosedependent manner. Their combination produced greater growth inhibition than when either was used alone（P<0.01）. Gefitinib and Celecoxib both induced apoptosis of A549 cells, and their combination produced a higher apoptosis rate（P<0.01）. Gefitinib in combination with Celecoxib also induced G1 phase arrest and down regulated expressions of EGFR and COX2 in A549 cells（P<0.05）.　ConclusionsGefitinib in combination with Celecoxib can promote a cooperative effect and synergistic cell growth inhibition.

Key words: Gefitinib； Celecoxib; Cell Apoptosis; Epidermal Growth Factor Receptor; Cyclooxygenase2

中图分类号:

R734

. 吉非替尼联合塞来昔布对肺腺癌细胞凋亡和EGFR、COX2表达的影响[J]. 山东大学学报(医学版), 2009, 47(8): 37-41.

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