他克莫司对肝癌细胞增殖、凋亡及其对5-氟尿嘧啶敏感性的影响  

Effect of tacrolimus on the proliferation,apoptosis,and fluorouracil sensitivity in hepatocellular carcinoma

作　　者：曹晓伟[1] 傅志仁[1] 丁国善[1] 王正昕[1] 郭闻渊[1] 李先兴[1] 付宏[1] 倪之嘉[1] 施晓敏[1] 马钧[1] 陈小松[1] 

机构地区：[1]第二军医大学长征医院肝移植中心解放军器官移植研究所,上海200003

出　　处：《中华实验外科杂志》2005年第5期544-546,共3页Chinese Journal of Experimental Surgery

摘　　要：目的探讨他克莫司(FK506)对肝癌细胞增殖、凋亡及其对5-氟尿嘧啶(5-Fu)敏感性的影响及其机制。方法体外培养人肝癌细胞株SMMC-7721,采用噻唑蓝(MTT)比色法检测FK506对细胞增殖的影响;应用流式细胞术分析FK506、5-Fu及联合FK506和5-Fu对SMMC-7721细胞周期和凋亡的影响。结果FK506(10、100、1000μg/L)对肝癌SMMC-7721细胞的增殖有抑制作用(P<0.05),但作用24h后各组凋亡率与对照组比较,差异无统计学意义(P>0.05);5-Fu(50、75、100、200mg/L)作用24h后,其诱导细胞凋亡率呈浓度依赖关系,分别为13.2%、15.3%、21.7%和35.9%,与对照组相比,差异有统计学意义(P<0.001);随着5-Fu用药浓度的增加,S期细胞比例和细胞增殖指数也增加;FK506预处理增强了5-Fu诱导SMMC-7721细胞凋亡的作用,24h细胞凋亡率分别为27.6%、32.0%和39.0%。结论FK506能够显著抑制肝癌SMMC-7721细胞增殖,并能增强该细胞系对5-Fu的敏感性,这一作用可能与FK506和5-Fu协同诱导凋亡和G0/G1期停滞有关。Objective To investigate the effect and its mechanism of tacrolimus (FK506) on the proliferation,apoptosis,and fluorouracil(5-Fu) sensitivity in hepatocellular carcinoma.Methods The SMMC-7721 cells used in the experiment were cultured in vitro,and the MTT assay was used to examine the antiproliferative effect of FK506;Flow cytometry (FCM) was used to examine the effects of FK506 in the presence or absence of 5-Fu on the apoptosis and cell cycle of SMMC-7721 cells.Results FK506 produced concentration-dependent antiproliferative effects at all experimental concentrations in SMMC-7721 cells (P< 0.05), but had no effect on induction of apoptosis;5-Fu could induce apoptosis in a concentration-dependent manner,and the percentage of G_0/G_1-phase cells and proliferation index (PI) were increased with the concentration of 5-Fu;Pretreatment with FK506 for 1.5 h could enhance the effect of 5-Fu inducing apoptosis.Conclusion FK506 can inhibit the growth of SMMC-7721 and enhance its 5-Fu sensitivity.This may be associated with the synergic effect between FK506 and 5-Fu inducing apoptosis and G_0/G_1-phase arrest.

关 键 词：肝癌细胞增殖 5-氟尿嘧啶 他克莫司 敏感性 肝癌SMMC-7721细胞 FK506 5-Fu 细胞凋亡率 人肝癌细胞株 细胞增殖指数 S期细胞比例 流式细胞术 24h 体外培养 细胞周期 抑制作用 浓度依赖 用药浓度 诱导凋亡 对照组 统计学 

分 类 号：R735.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]