Effect of lumiracoxib on proliferation and apoptosis of human aonsmall cell lung cancer cells in vitro  

作　　者：HAO Ji-qing LI Qi XU Shu-ping SHEN Yu-xian SUN Gen-yun 

机构地区：[1]Department of Geriatrics, First Affliated Hospital of AnhuiMedical University, Hefei, Anhui 230022, China [2]Key Laboratory of Gene Resource Utilization for Genetic Diseasesof Ministry of Education and Anhui Province, Anhui MedicalUniversity, Hefei, Anhui 230032, China

出　　处：《Chinese Medical Journal》2008年第7期602-607,共6页中华医学杂志（英文版）

基　　金：This work was supported by grants from the Natural Science Foundation of Anhui Province （No. 07021008） and the General Project of the Natural Science Foundation of the Department of Education, Anhui Province （No. KJ2007B142）.

摘　　要：Background Lumiracoxib is a highly selective cyclooxygenase-2 （COX-2） inhibitor with antiinflammatory, analgesic and antipyretic activities comparable with class specific drugs, but with much improved gastrointestinal safety. No studies have examined lumiracoxib for antitumorigenic activity on human nonsmall cell lung cancer cell lines in vitro or its possible molecular mechanisms. Methods The antiproliferative effect of lumiracoxib alone or combined with docetaxol on A549 and NCI-H460 lines was assessed by 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） assay. Drug-drug interactions were analyzed using the coefficient of drug interaction （CDI） to characterize the interactions as synergism, additivity or antagonism. Morphological changes were observed by acridine orange fluorescent staining. Extent of apoptosis was determined by flow cytometry. Results Lumiracoxib （15-240 pmol/L） has an inhibitory effect on the proliferation of A549 and NCI-H460 cell lines in concentration- and time-dependent manners with the ICso values of 2597 pmol/L and 833 pmol/L, respectively. The synergistic effect was prominent when lumiracoxib （15-240 pmoVL） was combined with docetaxol （0.2-2 pmol/L） （CDI 〈1）. Fluorescent staining showed that lumiracoxib could induce apoptosis in A549 and NCI-H460 cells. Lumiracoxib treatment also caused an increase of the sub-G1 fraction in each cell line and resulted in an increase of G0/Gl-phase cells and a decrease of S-phase cells. Conclusions Lumiracoxib had antiproliferative effect on the human nonsmall cell lung cancer cell lines A549 and NCI-H460 and had a significant synergy with docetaxol, which may be related to apoptotic induction and cell cycle arrest.Background Lumiracoxib is a highly selective cyclooxygenase-2 （COX-2） inhibitor with antiinflammatory, analgesic and antipyretic activities comparable with class specific drugs, but with much improved gastrointestinal safety. No studies have examined lumiracoxib for antitumorigenic activity on human nonsmall cell lung cancer cell lines in vitro or its possible molecular mechanisms. Methods The antiproliferative effect of lumiracoxib alone or combined with docetaxol on A549 and NCI-H460 lines was assessed by 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） assay. Drug-drug interactions were analyzed using the coefficient of drug interaction （CDI） to characterize the interactions as synergism, additivity or antagonism. Morphological changes were observed by acridine orange fluorescent staining. Extent of apoptosis was determined by flow cytometry. Results Lumiracoxib （15-240 pmol/L） has an inhibitory effect on the proliferation of A549 and NCI-H460 cell lines in concentration- and time-dependent manners with the ICso values of 2597 pmol/L and 833 pmol/L, respectively. The synergistic effect was prominent when lumiracoxib （15-240 pmoVL） was combined with docetaxol （0.2-2 pmol/L） （CDI 〈1）. Fluorescent staining showed that lumiracoxib could induce apoptosis in A549 and NCI-H460 cells. Lumiracoxib treatment also caused an increase of the sub-G1 fraction in each cell line and resulted in an increase of G0/Gl-phase cells and a decrease of S-phase cells. Conclusions Lumiracoxib had antiproliferative effect on the human nonsmall cell lung cancer cell lines A549 and NCI-H460 and had a significant synergy with docetaxol, which may be related to apoptotic induction and cell cycle arrest.

关 键 词：cyclooxygenase-2 inhibitors LUMIRACOXIB docetaxol lung cancer APOPTOSIS cell cycle 

分 类 号：R734.2[医药卫生—肿瘤]