三氧化二砷对人胃癌裸鼠皮下移植瘤的作用机制  

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

作　　者：梁军[1] 高永丽[1] 赵园园[1] 姚如永[1] 尚庆军[1] 高士芳[1] 胡晓晓[1] 

机构地区：[1]青岛大学医学院附属医院肿瘤科,山东青岛266003

出　　处：《第四军医大学学报》2007年第8期700-702,共3页Journal of the Fourth Military Medical University

基　　金：国家中药管理局资助项目(00-01LL13)

摘　　要：目的:探讨不同剂量As203对人胃癌细胞株SGC-7901裸鼠皮下移植瘤的体内抑瘤作用及作用机制.方法:建立人胃癌裸鼠皮下移植瘤模型,随机分为实验组即As203低(1.0mg/kg)中(2.5mg/kg)高(5.0mg/kg)剂量组、空白对照生理盐水组及阳性对照5-FU组(20mg/kg),腹腔连续给药10d,计算抑瘤率,检测用药后裸鼠的肝肾功能及血常规,观察用药前后裸鼠体重改变,实时定量RT-PCR检测移植瘤内caspase-3基因相对表达量.结果:低剂量As203组及5-FU组抑瘤率分别为60.6%和78.2%,与生理盐水组比较有统计学差异(P<0.05),中高剂量组及5-FU组差异无统计学意义(P>0.05).用药后低剂量As203组caspase-3的基因表达显著增高,与生理盐水组比较有统计学意义(P<0.05),中高剂量组在数值上caspase-3表达增高,但无统计学差异(P>0.05).各剂量组均出现白细胞抑制,但较5-FU组轻,肝肾功能未见异常.结论:低剂量As203表现出抑制肿瘤生长的作用,其机制可能与上调caspase-3基因的表达有关;As203对肝肾无明显毒性.AIM： To study the effect and mechanism of arsenic trioxide （As2O3 ） at different concentrations on human gastric SCG-7901 cells implanted under the skin of nude mice in vivo, as well as the related toxicity. METHODS： The subcutaneously transplanted tumor models of human gastric carcinoma in nude mice were established and then were divided at random into 5 groups：1. 0, 2.5 and 5.0 mg/kg As2O3,saline and 5-FU （20 mg/kg）, each of which was composed of 5 nude mice and then received intraperitaneal injection in the following 10 d. The tumor inhibition rate was calculated and the gene expression of caspase-3 was detected by the real-time RT-PCR. The weight detection of pre- and post-administration, blood routine examination and hepatic and nephritic functional examination were carried out to evaluate the side effects of As2O3. RESULTS： 1.0 mg/kg As2O3 and 5-FU could obviously inhibit the growth of transplanted tumor with the tumor inhibitory rate of 60.6% and 78.2%, respectively; in contrast to the saline group, the differences were significant （P 〈 0.05）. No significant difference was found in tumor inhibition rates among 2.5, 5.0 mg/kg As2O3 groups, 5-Fu group and saline group （P 〉 0.05 ）. As2O3 showed the less haematological toxicity than 5-FU, and without hepatic and nephritic toxicity. The expression of caspase-3 was up-regulated obviously in the 1.0 mg/kg As2O3 group in contrast to the saline group with the statistic difference（ P 〈 0. 05 ）. However, the expression of caspase-3 showed no difference among the groups of 2.5 mg/kg, 5.0 mg/kg and saline（P 〉 0.05 ）. CONCLUSION： As203 at the concentration of 1.0 mg/kg could obviously inhibit the growth of the subcutaneous transplanted tumor of human grastric carcinoma in nude mice by up-regulating the expression of caspase-3 with the moderate white blood cell inhibition and without the hepatic and nephritic toxicity.

关 键 词：三氧化二砷 胃肿瘤 小鼠 裸 肿瘤移植 半胱氨酸天冬氨酸蛋白酶-3 

分 类 号：R73-361[医药卫生—肿瘤]