三氧化二砷和胂酸基乙酸体外抗癌作用的比较

背景与目的:近来,有研究表明某些有机砷诱导细胞凋亡的能力强于无机砷,胂酸基乙酸(arsacetyl,ASAC)为有机砷的一种。本研究比较三氧化二砷(As2O3)和ASAC对肝癌细胞的抑制作用及诱导凋亡作用。方法:采用MTT(methythiazolyltetrazolium)法和细胞凋亡检测法观察As2O3和ASAC对SMMC-7721细胞增殖的影响及作用机制;用MTT法检测药物对正常血管内皮细胞(VEC)毒副作用。结果:As2O3和ASAC都明显抑制细胞增殖,抑制作用呈时间和浓度依赖性,且ASAC的抑制作用明显强于As2O3。如药物作用48h,0.1μmol/LAs2O3组抑制率为(14.2±1.5)%,0.1μmol/LASAC组为(27.1±3.0)%。1μmol/LAs2O3和0.1μmol/LASAC对VEC几乎无毒副作用,同样条件下作用于SMMC-7721细胞株,有凋亡小体生成,凝胶电泳出现DNA梯度图谱,流式细胞检查见明显的凋亡峰出现,并使细胞周期阻滞在S+G2/M期。结论:As2O3和ASAC都可以在体外诱导肝癌细胞凋亡,且ASAC诱导凋亡的能力强于As2O3,两者都作用于G0/G1期细胞。

Comparison of antitumor efficacy between arsacetyl and arsenic trioxide in vitro

BACKGROUND & OBJECTIVE: Recently, it was reported that some organic arsenics was stronger than inorganic arsenics in inducing carcinoma cell apoptosis. This study was designed to compare arsacetyl (ASAC), a kind of organic arsenics, with As2O3 in the effect of inhibiting proliferation and inducing apoptosis in carcinoma cells. METHODS: MTT (Methythiazolyl tetrazolium) assay and analysis of apoptosis were used to evaluate the effects of arsacetyl and As2O3 on the proliferation of SMMC-7721 and their mechanisms. Their toxicity to vessel endothelium cells (VECs) was also determined by using MTT method. RESULTS: Both As2O3 and arsacetyl significantly inhibited the proliferation of SMMC-7721, the inhibitory effect was dose- and time-dependent and arsacetyl was stronger than As2O3 e.g. inhibitory ratio: (14.2 +/- 1.5)%, treated with 0.1 mumol/L arsacetyl for 48 h; (27.1 +/- 3.0)%, treated with 0.1 mumol/L arsacetyl for 48 h]. 1 mumol/L As2O3 and 0.1 mumol/L arsacetyl almost had no toxicity to VEC, while they induced SMMC-7721 apoptosis indicated morphologically by "small apoptopic body" formation; DNA ladders appeared on agarose gel electrophoresis. The flow cytometry assay indicated that most of the cells were arrested in S + G2/M phase and the apoptotic peak appeared. CONCLUSION: The ability of arsacetyl inducing apoptosis was stronger than As2O3, and SMMC-7721 in the G0/G1 phase may be the target of drug action.