三氧化二砷对人胃癌裸鼠皮下移植瘤的作用机制

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(1.0 mg/kg)中(2.5 mg/kg)高(5.0 mg/kg)剂量组、空白对照生理盐水组及阳性对照5-FU组(20 mg/kg),腹腔连续给药10 d,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.

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

AIM: To study the effect and mechanism of arsenic trioxide (As203 ) 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 As203,saline and 5-FU (20 mg/kg), each of which was composed of 5 nude mice and then received intraperitoneal 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 As203. RESULTS: 1.0 mg/kg As203 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 As203 groups, 5-Fu group and saline group (P>0.05). As203 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 As203 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.