咖啡因对喜树碱诱导Molt-4细胞凋亡的影响  

Effect of Caffeine on Camptothecin-induced Apoptosis of Molt-4 Cells

作　　者：谭惠玲[1] 冯永东[1] 陶德定[1] 肖徽[1] 谢大兴[1] 余从年[1] 龚建平[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院分子医学中心,湖北武汉430030

出　　处：《癌症》2005年第12期1479-1483,共5页Chinese Journal of Cancer

基　　金：国家自然科学基金资助项目(No.39670265;No.39730270;No.39725027);国家973肿瘤计划资助项目(No.G1998051212);卫生部临床重点学科(No.20012537)~~

摘　　要：背景与目的:有报道认为咖啡因(caffeine)可以作用于细胞周期检测点,从而影响细胞周期的进程,而这种效应对于肿瘤细胞凋亡的影响尚存在争议。本研究探讨咖啡因对喜树碱诱导Molt-4细胞凋亡的作用及其对细胞周期检测点的效应。方法:用喜树碱诱导细胞凋亡,以咖啡因作为干扰细胞周期检测点的因素。用API法(AnnexinⅤ-propidiumiodide,AnnexinⅤ/PI)及亚G1峰法对细胞凋亡率以及凋亡发生的周期特异性进行检测分析。结果:2.0～20.0mmol/L的咖啡因对处于对数生长期Molt-4细胞增殖没有影响。喜树碱能诱导Molt-4细胞产生以S期细胞为主的细胞周期特异性凋亡,0.15μmol/L喜树碱作用4、6h,细胞凋亡率分别为(23.69±2.26)%、(36.99±1.42)%;10.0mmol/L咖啡因能显著抑制这种细胞凋亡,与0.15μmol/L喜树碱联合作用4、6h后,细胞凋亡率分别下降至(4.79±0.64)%和(2.69±0.56)%。去除咖啡因后,凋亡细胞明显增多,去除4、6h后细胞凋亡率升至(46.23±0.21)%和(55.81±0.41)%,且仍以S期细胞为主。结论:咖啡因可以抑制喜树碱诱导细胞凋亡。作为影响细胞周期检测点的药物,咖啡因可以明显屏蔽检测点对损伤细胞的监督,抑制细胞凋亡,但其作用是一过性的、可以逆转的。BACKGROUND ＆ OBJECTIVE： Caffeine could act on cell cycle checkpoints and affect the progression of cell cycle, but its impact on apoptosis of tumor cells is in debate. This study was carried out to investigate the effects of caffeine on camptothecin-induced apoptosis and cell cycle checkpoints of leukemia cell line Molt-4. METHODS： The cell apoptosis was induced by camptothecin, and caffeine was used to interfere with cell cycle checkpoints. The apoptosis rate and cell cycle during apoptosis were analyzed using sub-G1 method and Annexin V-propidium iodide （Annexin V/PI） staining. RESULTS： Caffeine （2.0-20.0mmon/L） had no effecton proliferation of Molt-4 cells in exponentially growth phase. Camptothecin selectively induced apoptosis of Molt-4 cells in S phase; when induced with camptothecin （0.15 μmol/L） for 4 or 6 h, the apoptosis rates were （23.69±2.26）% and （36.99±1.42）%. This cell cycle-specific apoptosis were inhibited obviously by caffeine with the apoptosis rates of （4.79±0.64）% and （2.69±0.56）%. When caffeine was removed, the apoptosis rates increased obviously to （46.23±0.21）% and （55.81±0.41）%, and still mainly happened in S phase. CONCLUSIONS： Caffeine could inhibit camptothecin-induced apoptosis of Molt-4 cells. As a drug acting on cell cycle checkpoints, caffeine could transiently shield the surveillance of checkpoints to damaged cells and inhibit cell apoptosis. The effect may be reversed when caffeine is removed away.

关 键 词：咖啡因 喜树碱 MOLT-4细胞 细胞周期检测点 细胞凋亡 

分 类 号：R96[医药卫生—药理学]