[Effect of anti-vascular endothelial growth factor antibody on the progression of human gastric cancer orthotopic xenotransplanted into nude mice]

Abstract

Objective: To study the inhibiting effect of anti-vascular endothelial growth factor (VEGF) on the growth and metastasis of gastric cancer.

Methods: The anti-tumor and anti-metastasis effect of anti-VEGF antibody, mitomycin C (MMC) were investigated by means of an orthotopic xenotransplanted model of human gastric cancer SGC-7901 in nude mice which had been randomly divided into 4 groups: control group receiving PBS, group receiving 50 microg/mice anti-VEGF antibody, group receiving 2 mg/kg MMC, and group receiving 50 microg/mice anti-VEGF antibody combined with 2 mg/kg MMC. Anti-VEGF antibody was given i.p. twice a week and MMC was administered i.p. once 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 intra-tumoral microvessel density (MVD) was recorded, and the liver was histologically examined in order to discover micrometastasis.

Results: Both anti-VEGF antibody and MMC showed a significant inhibitory effect on the growth of primary tumors; in the combination treatment group the inhibitory effect was more significant than single agent. Liver metastasis developed in 19 of 28 mice (67.9%) of the controls and in 6 of 11 mice (54.5%) receiving MMC. In contrast, liver metastasis occurred in 2 of 10 mice (20%) receiving anti-VEGF antibody and none receiving combination treatment. In addition, the MVD was less significant in the anti-VEGF antibody group and combination treatment group than other groups.

Conclusions: Anti-VEGF may provide a new approach to the treatment of gastric cancer by inhibiting tumor angiogenesis, and combination of anti-VEGF antibody with MMC could be more effective.