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.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2005年第5期544-546,共3页
Chinese Journal of Experimental Surgery
