三氧化二砷对人胃癌裸鼠移植瘤血管生成素-2和血管内皮生长因子表达的影响

Effect of arsenic trioxide on angiopoietin-2 and VEGF expression in human gastric cancer transplanted in nude mice

目的研究三氧化二砷(As2O3)对肿瘤血管生成素-2(Ang-2)和血管内皮生长因子(VEGF)表达的影响。方法用人胃腺癌细胞株SGC7901接种30只裸鼠皮下,建立实体瘤模型;然后随机分为As2O3高剂量(5mg/kg)、低剂量(2.5mg/kg)治疗组和对照组,每组各10只。治疗组接受As2O3腹腔注射10d,对照组注射生理盐水。测量肿瘤体积并计算抑瘤率;免疫荧光标记CD31并计算血管密度;免疫组化方法测定Ang-2的表达;免疫荧光激光共聚焦检测VEGF的表达。结果砷剂治疗可抑制瘤块生长,2.5mg/kg和5mg/kgAs2O3治疗组的抑瘤率分别为30.33%和50.85%。As2O3治疗组的微血管密度(MVD)、VEGF荧光表达水平均显著低于对照组(P<0.01)。Ang-2主要在血管内皮细胞的胞浆中呈强阳性表达,可清晰标记肿瘤内的血管;对照组和As2O3治疗组血管内皮细胞Ang-2表达强度无明显差异。结论As2O3对Ang-2表达无明显影响,在As2O3治疗抑制瘤细胞VEGF表达的情况下,Ang-2表达可促进血管的退化。Ang-2主要在新生的内皮细胞表达,故可能作为新生血管的标记物,成为肿瘤新生血管研究的新指标。

Objective To investigate the effect of arsenic trioxide （As2 O3） on expression of angiopoietin-2 and vascular endothelial growth factor （VEGF） in cancer. Methods The solid tumor model was formed in nude mice with gastric cancer cell line SGC-7901. The 30 nude mice were randomly divided into the two arsenic-treated groups （2.5 mg/kg and 5 mg/kg） and control group. As2O3 was injected to mice in the treated groups for 10 days; the same volume of saline solution was injected to the control group. The volume of gastric tumor xenografts was measured and counted for tumor growth inhibition （TGI）. Microvessel density （MVD） labeled by CD31 was measured with immunofluorescence. Expression of angiopoietin-2 was detected by immunobistochemistry, and expression of VEGF was detected by immunofluorescence laser confocal technology. Results Tumor growth inhibitions were 30.33% and 50.85% in 2.5 mg/kg and 5 mg/kg As2O3, respectively. Decrease of MVD appeared in As2O3-treated tumors compared with that in the control group. The fluorescence intensity level of VEGF in tumor cells was lower significantly than that in the arsenic-treated groups. Angiopoietin-2 was mostly expressed in endothelial cells in tumors. There was no difference in expression level of angiopoeitin-2 between arsenic-treated groups and the control group. Conclusion As2O3 does not affect the expression of angiopoietin-2. Angiopoietin-2 may induce vessel regression, and VEGF expression is decreased by As2O3 in tumor. Angiopoietin-2 may become a new indicator in study on angiogenesis in tumor.