Combination Therapy with Vascular Endothelial Growth Factor Neutralizing Antibody and Mitomycin C on Human Gastric Cancer Xenograft

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Abstract
Antiangiogenic therapy has been proposed as a new strategy for the treatment of solid tumors. To enhance the therapeutic effect of antiangiogenic agents, combination with conventional anticancer therapy should be investigated. In the present study, we investigated the therapeutic effect of the combination of vascular endothelial growth factor neutralizing antibody (VEGF Ab) and mitomycin C (MMC) on MT‐2, a human gastric cancer xenograft. When small pieces of MT‐2 were transplanted orthotopically into 62 nude mice, liver metastasis developed 6 weeks after transplantation. The VEGF Ab (100 μg/mouse) was administered i.p. in the VEGF Ab group (n=14) and the combination group (n=16) twice a week from day 10 after transplantation. MMC (2 mg/kg) was administered in the MMC group (n=16) and the combination group (n=16) on days 10, 17 and 24 after transplantation. Compared with the control group, in which saline solution was administered i.p., all three treatments inhibited tumor growth significantly and the effects of MMC and combination therapy were potent. Liver metastases were also inhibited significantly by the administration of VEGF Ab alone, MMC alone or combination therapy. Liver metastasis developed in 9 mice of the control group, 3 of the VEGF Ab group, and 4 of the MMC group, but no mice had liver metastasis in the combination therapy group. However a significant body weight loss and a decrease in spleen weight were observed in the MMC and combination groups, with no significant difference between the two groups. These results suggest that combination therapy with VEGF Ab and MMC may be a potent therapy for human gastric cancer.

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