机构地区:[1]河北省承德医学院附属医院肿瘤科,承德067000 [2]河北省承德医学院附属医院药学部,承德067000
出 处:《中国肿瘤临床与康复》2017年第5期545-548,共4页Chinese Journal of Clinical Oncology and Rehabilitation
摘 要:目的探讨沙利度胺联合表阿霉素抗人肝癌细胞HepG2体外增殖的影响,为肝癌治疗提供依据。方法采用人肝癌细胞株HepG2作为研究对象,共设4组:空白对照组、表阿霉素组(1.0 mg/L)、沙利度胺梯度组(50μg/ml、100μg/ml、200μg/ml和400μg/ml)和联合组(沙利度胺200μg/ml+表阿霉素1.0 mg/L),观察4组用药方案12h、24h、48h和72h时对HepG2细胞的影响,采用四甲基偶氮唑盐微量酶反应比色法(MTT)检测细胞增殖抑制效果,采用流式细胞术检查细胞凋亡情况。结果 MTT结果显示,沙利度胺能够有效的抑制HepG2细胞的增殖,且具有剂量和时间依赖性。作用时间为12h,24h和48h时,沙利度胺浓度为200μg/ml的抑制率最高,与其他各浓度比较,差异有统计学意义(P<0.05)。作用时间为48h时,除50μg/ml外的其他浓度的沙利度胺的抑制率最高,与其他各时间比较,差异有统计学意义(P<0.05)。沙利度胺200μg/ml浓度组和联合组各时间点对HepG2细胞的抑制率比较,差异有统计学意义(P<0.05)。各时间点时,联合组的抑制率高于沙利度胺200μg/ml浓度组和表阿霉素组,差异有统计学意义(P<0.05)。沙利度胺200μg/ml浓度组和联合组的抑制率,48h时最高,与其他各时间点比较,差异有统计学意义(P<0.05)。流式细胞术检验结果显示,作用时间为12h和24h时,沙利度胺梯度组对HepG2细胞凋亡指数(AI)影响的比较,差异有统计学意义(P<0.05)。沙利度胺浓度为50μg/ml、100μg/ml和200μg/ml时,HepG2细胞凋亡指数比较,差异有统计学意义(P<0.05)。各时间点,表阿霉素组、沙利度胺梯度组和联合组对HepG2细胞AI的比较,且联合组的抑制率显著高于其他各组,差异均有统计学意义(均P<0.05)。结论沙利度胺具有体外抑制人肝癌细胞株HepG2增殖和促凋亡作用,具有剂量和时间依赖性,可使用沙利度胺联合表阿霉素治疗肝癌。Objective To investigate the synergistic effect of thalidomide combined with epirubicin on the in vitro proliferation of human hepatoma cell line HepG2, and to provide basis for the treatment of liv- er cancer. Methods Human hepatocellular carcinoma cell line HepG2 was used as the study sugjects which were classified into 4 groups : blank control group, epirubicin group ( 1.0 mg/L), thalidomide gradi- ent group (50 μg/ml, 100 μg/ml, 200 μg/ml and 400 μg/ml) and combined group (thalidomide 200μg/ ml + epirubicin 1.0 mg/L). The effects of different therapeutic schemes and the effect on HepG2 cells at 12h, 24h, 48h and 72h were observed. Methyl thiazolyl tetrazolium MTT colorimetric assay was used to de- tect the efficacy of cell proliferation inhibition, and the apoptosis was detected by flow cytometry. ResultsMTT results showed that thalidomide could effectively inhibit the proliferation of HepG2 cells in a dose-and time-dependent manner, with the highest inhibitory rate at 200 μg/ml at 12h, 24h and 48h ( (P 〈0. 05). The inhibitory rate was the highest at 48 h except 50μg/ml (P 〈 0.05 ). There was significant difference in inhibitory rate of HepG2 cells between thalidomide 200μg/ml group and the combined group at each time point (P 〈 0. 05 ). At each time point, inhibitory rate in the combined group was higher than thalidomide 200μg/ml group and epirubicin group (P 〈 0. 05 ). Flow cytometry test reavealed that there was significant difference in apoptosis index (AI) of HepG2 among different thalidomide group at 12h and 24h (P 〈 0. 05 ). There was significant difference in AI among epirubicin group, thalidomide gradient group and com- bined group at different time points, with the highest inhibition rate in the combined group (P 〈 0.05 ). Conclusion Thalidomide can inhibit in vitro proliferation and promote apoptosis of HepG2 cells and in a dose-and time-dependent manner. The combination of thalidomide and epirubicin can be used in the treatment of
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