选择性环氧合酶-2抑制剂对结肠癌细胞的 生长抑制作用及机制探讨(英文)  

Growth-inhibitory effects of selective cyclooxygenase-2 inhibitor on colon cancer cells and its possible mechanisms

作　　者：贾晓青[1] 韩丽辉[2] 钟宁[1] 孟繁立[1] 阎明[1] 李文捷[1] 李延青[1] 张尚忠[1] 

机构地区：[1]山东大学齐鲁医院消化科,山东济南250012 [2]山东大学医学院免疫学研究所,山东济南250012

出　　处：《中国病理生理杂志》2005年第5期985-989,共5页Chinese Journal of Pathophysiology

摘　　要：目的研究NS-398(一种选择性环氧合酶-2抑制剂)对结肠癌HT-29细胞的生长抑制作用并探讨其机制。方法通过MTT法检测细胞的增殖情况,通过流式细胞术检测细胞凋亡率和细胞周期,通过RT-PCR检测bcl-2mRNA和baxmRNA表达,通过共聚焦激光扫描显微镜观察细胞骨架成分F-actin的变化。结果NS-398 对结肠癌HT-29细胞生长的抑制具有时间和剂量依赖性。流式细胞术结果显示NS-398可剂量依赖地诱导HT- 29细胞凋亡,使其停滞于G0/G1期。经不同浓度的NS-398处理72h后,bcl-2mRNA在HT-29细胞的表达降低, bcl-2/bax比值降低。细胞骨架成分F-actin主要分布在HT-29细胞核周围,呈环状结构,NS-398作用后细胞核周围的环状结构消失。结论NS-398可显著抑制结肠癌细胞的体外生长并诱导其凋亡,这与下调bcl-2/bax比值以及细胞骨架的破坏有关。AIM: To evaluate the growth-inhibitory effects of NS-398, a selective cyclooxygenase-2 inhibitor, in human colon cancer HT-29 cells and its possible mechanisms. METHODS: MTT assay was applied to detect the cell proliferation. Flow cytometry was performed to detect apoptosis rate and cell cycle. RT-PCR was used to detect the expression of bcl-2 mRNA and bax mRNA. Alteration of cytoskeleton component F-actin was observed by confocal laser scanning microscope. RESULTS: NS-398 could inhibit growth of HT-29 cells in dose-and time-dependent manners. Flow cytometry revealed that NS-398 could induce apoptosis and cause G_0/G_1 arrest of HT-29 cells in a dose-dependent manner. After 72 h incubation with NS-398 at different concentrations, the expression level of bcl-2 mRNA was lowered and the ratio of bcl-2 to bax was decreased in HT-29 cells. F-actin was mainly distributed around nuclei forming annular structure in HT-29 cells. After exposure to NS-398, the annular structure around nuclei disappeared and fluorescence intensity of F-actin decreased obviously. CONCLUSION: NS-398 can inhibit the growth effectively and induce apoptosis in HT-29 cells in vitro, which is associated with the down-regulation of bcl-2 to bax ratio and the disruption of cytoskeleton.

关 键 词：环加氧酶抑制剂 细胞凋亡 结肠肿瘤 

分 类 号：R735.35[医药卫生—肿瘤]