三氧化二砷粉针剂联合重组腺病毒介导的IκBαM治疗肝癌

Inhibitory effect of As_2 O_3 combined with adenovirus carrying IκBαM on proliferation of liver cancer cells in vitro and in vivo

目的:探讨三氧化二砷(arsenic trioxide,As2O3)粉针剂联合重组腺病毒介导的IκBαM抑制肝癌细胞增殖及对大鼠肝癌的治疗效果.方法:MTT法检测不同浓度As2O3联合Ad-IκBαM对肝癌细胞增殖的抑制作用.探讨体内As2O3联合Ad-IκBαM对二乙基亚硝胺诱发的大鼠肝癌的抑制作用,并应用TUNEL法检测各处理组肝癌的凋亡指数.结果:As2O3处理肝癌细胞SMMC-7721的细胞毒作用存在剂量依赖性以及时间依赖性,16 mol/L的As2O3抑制率最高,48、72、96 h分别为17.7%±5.3%、40.7%±2.5%、62.8%±5.4%.16 mol/L As2O3联合转染Ad-IκBαM处理组在72 h和96 h,对肝癌细胞抑制率分别为68.3%±2.1%和81.9%±3.0%,显著高于16μmol/L As2O3联合Ad-I B组(P值分别为0.004).二乙基亚硝胺于第16周诱发大鼠肝癌,成瘤率约达80%.各处理组成瘤大鼠(包括无菌生理盐水组、As2O3组、As2O3+Ad-I B组以及As2O3+Ad-IκBαM组)的生存期无明显差别.As2O3联合Ad-IκBαM处理组肝癌的凋亡率较其他处理组均显著增高.结论:腺病毒介导的IκBαM与As2O3具有协同作用,转染Ad-IκBαM可以明显增强As2O3的抑制肝癌细胞增殖作用以及体内抑瘤作用.

AIM：To analyze the inhibitory effect of arsenic trioxide（As2O3） combined with adenovirus carrying IκBαM（Ad-IκBαM） on proliferation of liver cancer cells in vitro and in vivo.METHODS：The effect of As2O3 combined with Ad-IκBαM on liver cancer cell growth was assessed by MTT assay.Wistar rats were treated with diethylnitrosamine（DENA） for about 16 wk to induce liver cancer.The index of apoptosis was assessed by TUNEL assay.RESULTS：As2O3 induced cellular toxicity in a dose-and time-dependent fashion in SMMC-7721cells.MTT assay showed that the proliferation of SMMC-7721 cells was most significantly suppressed by As2O3 at a dose of 16 mol/L,and the reduced rate of cell proliferation was 17.7%±5.3%,40.7%±2.5% and 62.8%±5.4% at 48,72 and 96 h,respectively.The reduced rate of cell proliferation at 72 and 96 h in cells treated with 16 mol/L As2O3 and Ad-IκBαM was 68.3%±2.1% and 81.9%±3.0%,significantly higher than those in other groups（all P0.01）.DENA treatment successfully induced tumors in rats at week 16.There was no significant difference in life span of liver cancer-bearing rats among each group.TUNEL assay demonstrated that treatment with As2O3 and Ad-IκBαM greatly enhanced apoptotic cell death.CONCLUSION：Ad-IκBαM has a synergistic effect with As2O3 in inhibiting liver cancer cell proliferation in vitro and in vivo.