全反式维甲酸联合三氧化二砷对人肝癌细胞株HepG2及其移植瘤的抑制作用

Inhibitory effects of all-trans-retinoic acid and arsenic trioxide on human hepatocarcinoma cell HepG2 and transplantation tumor

目的探讨全反式维甲酸(ATRA)联合三氧化二砷(As2O3)在体外和体内对肝癌细胞HepG2的抑制作用。方法将不同剂量的ATRA和As2O3单独及联合作用于体外培养的人肝癌细胞株HepG2,用MTT比色法分析两药物对肝癌细胞生长的体外抑制作用。建立人肝癌细胞HepG2移植瘤模型,观察ATRA联合As2O3的体内抑瘤作用。结果ATRA在体外对HepG2具有增生抑制作用,并呈现明显的剂量依赖性,10μmol/L的抑制率为(40.9±2.3)%,与As2O3联用产生协同作用,能明显增强其对HepG2的抑制作用,10μmol/L ATRA与1μmol/L As2O3联合应用抑制率达(62.7±2.5)%。体内实验显示,ATRA与As2O3单独及联合均能对HepG2移植瘤起到明显的抑制作用,联合应用组对实体瘤的瘤重和瘤体的抑瘤率分别为70.75%和70.02%,明显优于单独用药组。结论ATRA和As2O3在体外和体内对肝癌细胞HepG2的生长均有抑制作用,联合应用具有协同效应,抑瘤作用明显增强。ATRA和As2O3联合应用将来有望用于肝癌的临床治疗。

Objective To study the inhibition effects of all-trans-retinoic acid （ATRA） and arsenic trioxide （As2O3） on human hepatocarcinoma cell HepG2 in vitro and in vivo. Methods The inhibition effect of ATRA combined As2O3 on the grouth of cultured HepG2 cells was determined by MTT assay in vitro. The transplant tumor mouse model was used to observe the inhibition effects of ATRA and As2O3 on HepG2 cells in vivo. Results ATRA could inhibit the growth of cultured HepG2 cells in vitro in a dose-dependent manner. The inhibition rate was （40.9 ± 2.3） % at 10 μmol/L of ATRA. The combination of ATRA and As2O3 could obviously enhance the inhibition effects. The inhibition rate was （62.7 ± 2.5 ） % when 10 μmol/L ATRA was used with 1 μmol/L As2O3. The combination of ATRA and As2O3 also had significant anti-tumor activity in transplant hepatoma mice model. The inhibition rates were 70.75% （weight） and 70.02% （size）. Conclusion ATRA and As2O3 have marked inhibition effects on HepG2 cells both in vitro and in vivo. The combination of ATRA and As2O3 has synergistic action and can significantly enhance their inhibition effects.