As_2O_3对人胃癌细胞株SCG-7901裸鼠移植瘤的抗肿瘤机制研究

Anti-tumor mechanism analysis of arsenic trioxide on the subcutaneously transplanted tumor of human gastric carcinoma in nude mice

目的:探讨不同剂量的三氧化二砷(As2O3)对人胃癌细胞株SCG-7901裸鼠皮下移植瘤的抗肿瘤机制。方法:建立人胃癌裸鼠皮下移植瘤模型,随机分为实验组即As2O3低剂量组(1.0mg/kg)、As2O3中剂量组(2.5mg/kg)和As2O3高剂量组(5.0mg/kg),空白对照生理盐水组及阳性对照5-FU组(20mg/kg),分别腹腔连续给药10天,停药后24小时处死裸鼠,称取瘤重,计算抑瘤率,流式细胞仪检测凋亡率及Caspase-3的活性变化。结果:低剂量As2O3组及5-FU组抑瘤率分别为60.6%及78.2%,与生理盐水组比较均有统计学意义(P<0.05),低剂量组与5-FU组抑瘤率差异无统计学意义(P>0.05);高、中、低剂量As2O3组流式细胞仪检测时均出现典型凋亡峰,凋亡率分别为18.32%、17.86%、21.89%,同时伴有Caspase-3活性的增加,其中低剂量As2O3活性增加最显著。结论:低剂量As2O3在体内可通过活化Caspase-3诱导细胞凋亡而发挥抗肿瘤作用。

Objective：To study the machanism of arsenic trioxide at different concentration on human gastric cell line SCG- 7901 implanted under the skin of nude mice in vivo. Methods：The subcutaneous transplantable tumor model of human gastric carcinoma in nude mice were established and then were divided at random into five groups ： 1.0, 2. 5, 5. 0 mg/kg As2O3, saline and 5-FU group, each of which was composed of five nude mice and then received intraperitonal injection in the following ten days. The tumor inhibition rate was calculated to evaluate the anti-tumor effect. The apoptosis rate and the active caspase-3 were detected by the flow cytometer. Results： 1.0mg/kg As2O3 and 5-FU groups could obviously inhibit the growth of transplantable tumor with the tumor inhibitory rate of 48. 1% and 71.3% respectively. In contrast to the group of saline, the difference is significant（P 〈0.05） ,but the difference between 1.0mg/kg As2O3 and 5-FU group is not significant （P 〉 0. 05 ）. The apoptotic peak was observed in the As2O3 groups with the apoptosis rate 18.32%, 17.86%, 21.89% for the 1.0mg/kg, 2.5mg/kg and 5.0mg/kg As203group respectively and the increase of caspase-3 activity was observed in each As2 03 group. Conclusion：As2O3 could inhibit the growth of the human gastric subcutaneous transplantable tumor by regulating up the activity of Caspase-3 and inducing the cell apoptosis in vivo.