尼美舒利逆转Th1/Th2偏移调节胆管癌细胞增殖的机制研究  

Regulatory effects of Nimesulide on secreting Th1/Th2 cell cytokines on proliferation of human cholangiocarcinoma cell line in vitro

作　　者：孔琦[1] 黄强[2] 陈斌[1] 王道明[1] 朱家胜[1] 夏亚斌[1] KONG Qi;HUANG Qiang;CHEN Bin;WANG Dao-ming;ZHU Jia-sheng;XIA Ya-bin(Gastric&Intestine of General Surgery,Yijishan Hospital,Affiliated Hospital of Wannan Medical College,Wuhu 241000,China;Dept.of General Surgery,Anhui Provincial Hospital,Hefei 230032,China)

机构地区：[1]皖南医学院弋矶山医院胃肠一科,安徽芜湖241000 [2]安徽省立医院普外科,安徽合肥230032

出　　处：《泰山医学院学报》2018年第11期1213-1216,共4页Journal of Taishan Medical College

基　　金：安徽省教育厅自然科学基金项目(KJ2008B083)

摘　　要：目的探讨选择性环氧合酶-2(cyclooxygenase-2,COX-2)抑制剂尼美舒利通过调节胆管癌细胞Th1/Th2细胞因子分泌抑制其生长的机制。方法应用MTT法观察尼美舒利对人胆管癌细胞增殖的影响,透射电镜检测细胞形态学改变,ELISA法检测胆管癌细胞株中IL-2、IL-4、IL-6和IFN-γ细胞因子的表达,流式细胞仪检测尼美舒利对Th1/Th2细胞因子分泌的影响。结果尼美舒利呈时间、剂量依赖性抑制胆管癌细胞增殖,并出现细胞凋亡形态学改变,不同浓度尼美舒利作用于胆管癌细胞后,随尼美舒利浓度升高,IL-2、IFN-γ浓度呈上升趋势,而IL-4、IL-6水平下降,Th1细胞阳性率升高,而Th2细胞呈下降趋势,Th1/Th2比值升高。结论胆管癌细胞呈Th2优势状态,尼美舒利通过逆转Th1/Th2偏移调节细胞免疫从而发挥抗肿瘤作用。Objective:To explore the regulatory effect of a selective inhibitor of COX-2 nimesulide on secreting Th1/Th2 cell cytokines on proliferation of cholangiocarcinoma cell line in vitro.Methods:The inhibitive effect of nimesulide on cholangiocarcinoma cell line HCCC-9810 was measured with MTT.Apoptosis was measured by transmission electron microscopy.IL-2,IL-4,IL-6 and IFN-γcytokines concerntrations were detected by ELISA considering IL-2 and IFN-γas Th1 cytokines and IL-4,IL-6 as Th2 ones.The changes of Th1/Th2 cytokines were analyzed by flow cytometry.Results:Nimesulide effects had a dose-dependent and time-dependent growth inhibition on HCCC-9810 cells.Morphologic features of apoptosis were seen by transmission electron microscopy.After being cultured with different concentration of nimesulide,the concentration of Thl/Th2 cytokines were changed obviously,which was reflected by a significant enhancement in IL-2 and IFN-γexpression paralleled by a substantial decrease in IL-4 and IL-6 with a dose-dependent manner.Th1 cells increased while Th2 cells decreased at the same time,this led to the obvious changes of Thl/Th2 ratio.Conclusion:The expression of Th1 cytokines is inhibited with a predominant state of Th2 cytokines in cholangiocarcinoma cell line.Nimesulide can convert the imbalance of Th1/Th2 cytokines and regulate cellular immunity to prevent tumor growth.

关 键 词：胆管肿瘤 药物筛选试验 抗肿瘤 TH1/TH2 细胞因子 

分 类 号：R734.2[医药卫生—肿瘤]