5-氨基水杨酸联合尼美舒利对结肠癌细胞株HT-29增殖的影响  

Effect of 5-Aminosalicylic Acid in Combination with Nimesulide on the Proliferation of Colonic Cancer Cell Line HT-29

作　　者：方海明[1] 梅俏[1] 马维娟[1] 许建明[1] 

机构地区：[1]安徽医科大学第一附属医院消化内科安徽省消化病重点实验室,安徽医科大学药理教研室230022

出　　处：《胃肠病学》2007年第4期228-232,共5页Chinese Journal of Gastroenterology

摘　　要：背景:研究表明5-氨基水杨酸(5-ASA)和非甾体抗炎药(NSAIDs)对结直肠癌具有化学预防作用,但目前关于两类药物联合应用对结直肠癌影响的文献较少。目的:研究5-ASA联合选择性环氧合酶-2抑制剂尼美舒利对人结肠癌细胞株HT-29的增殖抑制作用及其可能机制。方法:采用甲基噻唑基四唑(MTT)比色法测定5-ASA、尼美舒利单独以及联合应用抑制HT-29细胞增殖的作用,分别采用原位末端标记(TUNEL)和免疫细胞化学方法检测细胞凋亡和增殖细胞核抗原(PCNA)的表达。结果:1～1000μmol/L5-ASA或尼美舒利单独应用对体外培养的HT-29细胞具有明显增殖抑制作用,呈剂量依赖性;两者在100μmol/L剂量下分别作用12～96h,抑制率逐渐增高,呈时间依赖性。20～2000μmol/L5-ASA与尼美舒利联合应用能明显抑制HT-29细胞增殖,呈剂量和时间依赖性,且优于单独应用5-ASA或尼美舒利(P<0.05)。10～500μmol/L5-ASA和尼美舒利单独或联合作用于HT-29细胞,细胞凋亡率逐渐增高,PCNA表达逐渐降低,与单独应用相比,联合用药作用更强(P<0.05)。结论:5-ASA联合尼美舒利具有抗HT-29细胞增殖的作用,其作用优于单独应用5-ASA或尼美舒利。Background： Many studies have demonstrated that 5-aminosalicylic acid （5-ASA） and non-steroidal antiinflammatory drugs （NSAIDs） have chemoprevention effect on colorectal cancer. However, few studies have been published to date referring to the effect of coadministration of the two drugs. Aims： To investigate the inhibitory effect of 5-ASA in combination with nimesulide （a selective cyclooxygenase-2 inhibitor） on the proliferation of human colonic cancer cell line HT-29 and its potential mechanisms. Methods： The inhibitory effect of 5-ASA and/or nimesulide on HT-29 cells was determined by methyl thiazolyl tetrazolium （MTT） assay. Apoptosis and expression of proliferating cell nuclear antigen （PCNA） were detected by TdT-mediated dUTP-biotin nick-end labeling （TUNEL） assay and immunocytochemical staining, respectively. Results： After treatment with 5-ASA or nimesulide alone at the concentrations of 1 to 1000 μmol/L, the proliferation of HT-29 cells in vitro was inhibited in a dose-dependent manner. The inhibition rate increased in a timedependent manner when 100 μmol/L 5-ASA or nimesulide was used alone for 12 to 96 hours. The inhibitory effect of 5- ASA combined with nimesulide at the concentrations of 20 to 2000 μmol/L was better than 5-ASA or nimesulide used alone （P〈0.05） in a dose- and time-dependent manner. After treatment with 10 to 500 μmol/L 5-ASA combined with nimesulide, the apoptosis rate of HT-29 cells increased significantly, while PCNA expression decreased as compared with 5-ASA or nimesulide used alone at the same dosage （P〈0.05）. Conclusions： Combination of 5-ASA and nimesulide can inhibit the proliferation of HT-29 cells, and the inhibitory effect is better than 5-ASA or nimesulide used alone.

关 键 词：结肠肿瘤 HT29细胞 氨基水杨酸类 非甾类消炎药 

分 类 号：R735.35[医药卫生—肿瘤]