中文摘要：

目的探讨3-溴丙酮酸（3-BP）增强肝癌细胞对顺铂敏感性的作用及其可能机制。方法MTT法检测3-BP、顺铂对HepG2、SMMC7721细胞的增殖抑制作用。选择低于半数抑制浓度（IC50）的100μmol／L的3-BP和8μmol／L的顺铂单独或联合处理细胞，PI单染流式细胞术检测细胞凋亡，caspase3活性检测试剂盒测定caspase-3的活性变化，ATP检测试剂盒测定细胞内ATP水平，Western blot检测XIAP、PARP蛋白的表达。结果3-BP在50-400μmol／L浓度范围内对HepG2、SMMC7721细胞具有明显的增殖抑制作用（P〈0．01），作用48h的IC50分别为238．9±13．9μmol／L、278．7±11．7μmol／L；顺铂在2～32μmol／L浓度范围内对HepG2、SMMC7721细胞具有明显的增殖抑制作用（P〈0．01），作用48h的IC50分别为16．4±0．9μmol／L、20．9±1．8μmol／L。100μmol／L3-BP与8μmol／L顺铂联合作用于HepG2、SMMC7721细胞48h的增殖抑制率分别为（60．6±2．2）％、（56．8±2.3）％，明显高于对照组和单独用药组（P〈0．01）。100μmol／L3-BP与8μmol／L顺铂联合作用于HepG2、SMMC7721细胞48h的凋亡率分别为（51．1±4．3）％、（46．5±3．9）％，较单用3-BP、顺铂的凋亡率明显提高（P〈0．01）。结论3-BP能增强肝癌细胞HepG2、SMMC7721对顺铂诱导的凋亡的敏感性，其机制可能是通过引起细胞内ATP缺乏、下调XIAP蛋白的表达以及增加caspase-3的活性。

英文摘要：

Objective To investigate the effect of 3-bromopyruvate （3-BP） in sensitizing hepatoceUular carcinoma cells to cisplatin-induced apoptosis and its possible mechanism. Methods The growth inhibition of HepG2 and SMMC7721 cells following exposures to different concentrations of 3-BP and cisplatin was measured by MTT assay. The apoptosis of cells treated with 100 μmol/L 3-BP with or without 8 μmol/L cisplatin was assessed using flow cytometry with PI staining, and the activity of caspase-3 and intracellular ATP level were detected using commercial detection kits; the expression of XIAP and PARP was analyzed using Western blotting. Results 3-BP produced obvious inhibitory effects on HepG2 and SMMC7721 cells at the concentrations of 50-400 μmol/L with IC50 values of 238.9±13.9 μmol/L and 278.7±11.7 μmol/L for a 48-h treatment, respectively. Cisplatin also inhibited the growth of HepG2 and SMMC7721 cells at the concentrations of 2-32 μmol/L, with IC50 values of 16.4±0.9 μmol/L and 20.9±1.8 μmol/L after a 48-h treatment, respectively. Treatment with 100 μmol/L 3-BP combined with 8 μmol/L cisplatin for 48 h resulted in a growth inhibition rate of （60.6 ±2.2）% in HepG2 cells and （56.8 ± 2.3）% in SMMC7721 cells, which were significantly higher than those in cells treated with 3-BP or cisplatin alone. The combined treatment for 48 h induced an apoptotic rate of （51.1±4.3）% in HepG2 cells and （46.5±3.9）% in SMMC7721 cells, which were also markedly higher than those in cells with 3-BP or cisplatin treatment alone. Conclusion 3-BP can sensitize HepG2 and SMMC7721 cells to cisplatin-induced apoptosis possibly by causing intracellular ATP deficiency, down-regulating XIAP, and increasing caspase-3 activity.