As2O3对裸鼠移植肿瘤生长及血管生成的抑制作用
Inhibitory effect of arsenic trioxide on tumor growth and angiogenesis in nude mice bearing transplanted tumor
陈玺 1肖延风 1刘陕西 2邬德东 1任利芬1
作者信息
- 1. 第二附属医院儿科,陕西西安,710004
- 2. 第一附属医院血液科,陕西西安,710061
- 折叠
摘要
目的:研究三氧化二砷(As2O3)对人胃癌裸鼠皮下移植瘤微血管新生以及血管内皮生长因子受体-1(Fit-1)表达的抑制作用.方法:对30只裸鼠采用人胃腺癌SGC7901细胞建立皮下移植瘤模型,分为两个治疗组(2.5 mg/kg组和5mg/kg组)和对照组,每组10只.2.5 mg/kg组和5 mg/kg组给予As2O3腹腔沣射治疗,连续10 d.对照组注射生理盐水测定肿瘤重量、抑瘤率,以判定As2O3抑制肿瘤生长的效果;荧光免疫测定CD31并计算微血管密度(MVD);荧光免疫激光共聚焦测定Fit-1的表达.结果:2.5 mg/kg组,5 mg/kg组的抑瘤率按质量计算分别为29.08%和52.17%.As2O3治疗后瘤组织中MVD明显减少,与对照组比较差异有显著性意义(P<0.01);5 mg/kg组瘤块中MVD明显少于2.5 mg/kg组者(P<0.01).治疗组Flt-1表达显著低于对照组;5 mg/kg组瘤块中Fh-1明显少于2.5 mg/kg组者(P<0.01).结论:用As2O3单剂治疗能明显抑制人胃癌裸鼠皮下移植瘤的生长.As2O3治疗可显著减少肿瘤组织MVD,抑制肿瘤血管新生;抑制Fit-1的表达可能是As2O3抗肿瘤血管新牛的机制之一.
Abstract
AIM: To investigate the inhibitory effect of As2O3 on gastric tumor growth and angiogenesis and on the expression of Flt-1. METHODS: Solid tumor models were established in 30 nude mice with gastric cancer cell line SGC-7901. The mice were divided randomly into two treatment groups (5 mg/kg As2O3 and 2.5 mg/kg As2O3) and control group, with 10 in each group. As2O3 was injected to the arsenic-treatment groups (2. 5 mg/kg and 5 mg/kg) and the same volume of saline solution was injected to the control group. Tumor growth inhibition (TGI) was used to assess the inhibitory efficacy of As2O3 against xenografts. Mi-crovessel density (MVD) and Flt-1 were detected by immunofluo-rescence laser confocal microscopy. RESULTS: In 5 mg As2O3 and 2.5 mg As2 O3 treatment groups, the tumor growth inhibition rates were 29.08% and 52.17% respectively. Decrease of MVD was observed in As2O3 treatment tumors compared with that in control group(P<0.01). MVD in tumors was significantly lower in 5mg group than that in 2.5 mg group( P <0.01). The expression of Flt-1 was less in As2O3 treatment mice compared with that in controls, and less in 5mg As2O3 treatment group compared with that in 2. 5mg As2O3 treatment group ( P < 0. 01 ). CONCLUSION: As2O3 inhibits solid tumor growth and decreases MVD in tumors, possibly by inhibiting the expression of Flt-1.
关键词
三氧化二砷/肿瘤/抑瘤率/新生血管化,病理性/微血管密度/血管内皮生长因子受体-1Key words
arsenic trioxide/neoplasms/tumor growth inhibition/neovascularization, pathologic/microvessel density/vascular endothelial growth factor receptor-1引用本文复制引用
基金项目
陕两省自然科学基金(2002C239)
西安交通大学附属二院科研基金(2003-YL-35)
出版年
2009
NETL
NSTL
维普
万方数据