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

Effect of lumiracoxib on proliferation and apoptosis of human nonsmall cell lung cancer cells in vitro
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DOI:
10.1097/00029330-200804010-00006
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发表时间:
2008-04-05
影响因子:
6.1
通讯作者:
Sun Gen-Yun
Sun Gen-Yun
中科院分区:
医学2区
文献类型:
--
作者:
Hao Ji-Qing;Li Qi;Sun Gen-Yun

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背景:鲁米拉昔布是一种高度选择性的环氧合酶-2(COX-2)抑制剂,具有与一类特效药相当的抗炎、镇痛和解热活性,但大大改善了胃肠道的安全性。方法采用四甲基偶氮唑蓝(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑)比色法检测鲁米拉昔布单独或与多西紫杉醇合用对A549和NCI-H460细胞的增殖抑制作用。用药物相互作用系数(CDI)分析药物与药物的相互作用,将药物与药物的相互作用分为协同作用、相加作用或拮抗作用。丫啶橙荧光染色观察细胞形态变化。结果卢米拉昔布(15-240mU/L)对A549和NCI-H460细胞的增殖抑制作用呈浓度和时间依赖性,IC50值分别为2597mU/L和833mU/L。鲁米拉昔布(15-240mU/L)与多西紫杉醇(0.2-2mU/L)合用时,协同作用显著
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 mu mol/L) has an inhibitory effect on the proliferation of A549 and NCI-H460 cell lines in concentration- and time-dependent manners with the IC50 values of 2597 mu mol/L and 833 mu mol/L, respectively. The synergistic effect was prominent when lumiracoxib (15-240 mu mol/L) was combined with docetaxol (0.2-2 mu mol/L) (CDI