抗VEGF抗体及抗KDR抗体对裸鼠胃癌细胞增殖和凋亡的影响

The Effect of Anti-vascular Endothelial Growth Factor and Receptor Antibody on the Proliferation Activity and Apoptosis of Human Gastric Cancer

目的探讨抗VEGF抗体及抗KDR抗体对胃癌细胞增殖和凋亡的影响。方法建立胃癌原位种植模型;7天后注射抗VEGF抗体、抗KDR抗体及二者联合注射,连续给药8周,每周2次,第10周末处死动物,用免疫组化法、RT-PCR法检测移植瘤组织中VEGF蛋白和mRNA表达情况;FCM检测肿瘤细胞增殖及凋亡情况。结果与对照组相比,抗VEGF抗体和抗KDR抗体组肿瘤组织中VEGF蛋白的表达降低,而VEGFmRNA表达无显著变化;肿瘤细胞发生不同程度的凋亡,凋亡率明显增高,G0/G1期细胞明显增多,S期细胞明显减少,细胞增殖指数降低;两者合用时作用更为明显。结论通过中和VEGF抗体和封闭KDR受体抑制血管形成,可能为胃癌的抗血管生成治疗提供依据。

Objective To study the inhibiting effect of anti-vascular endothelial growth factor and receptor antibody on growth, metastasis and apoptosis of gastric cancer. Methods The inhibitory effect of antiVEGF antibody, anti-KDR antibody were investigated by means of an orthotopic xenotransplanted model of mice which had been randomly divided into 4 groups： ①control group, ②group receiving anti-VEGF antibody, ③group receiving anti-KDR antibody and ④group receiving anti-VEGF antibody and anti-KDR antibody. Anti-VEGF antibody and anti-KDR antibody was given i. p. twice a week for 8 weeks from day 7 after transplantation. All animals were sacrificed at the end of 10 weeks. The tumor was weighted and the expression level of VEGF mRNA and protein were examined in antisense group by RT-PCR analysis and immunohistochemistry respectively. Apoptotic cell and cell cycle were detected in transfected cells by FCM assay. Results The decreased expression levels of VEGF protein were found in anti-VEGF antibody group, anti-KDR antibody group, anti-VEGF antibody and anti-KDR antibody group. Apoptotic cells were found in three groups＇cells. G0/G1 phase cells were increased and S phase cells were decreased in cell cycle. Conclusions Both blockadiage of VEGF with anti-VEGF antibody and VEGF-binding site with anti-KDR antibody could inhibited gastric cancer, cells growth, which might provide a new approach to the treatment of gastric cancer.