[Effect of vascular endothelial growth factor antibody Avastin on angiogenesis of human gastric cancer growing orthotopically in nude mice]

Abstract

Background & objective: The failure to treat gastric cancer is often due to the recurrence or dismal metastasis of cancer and the poor response to traditional chemotherapeutic or radiotherapeutic regimens. Vascular endothelial growth factor (VEGF) is related closely to the growth and metastasis of gastric cancer. This study was to examine the effects of Avastin, a monoclonal antibody developed against VEGF, with or without 5-fluorouracil (5-FU) on the growth, metastasis, and angiogenesis of a gastric cancer model.

Methods: A metastasis model of human gastric cancer was established by orthotopic transplantation of histologically intact human tumor tissue blocks in the gastric walls of nude mice. All mice were randomly divided into 4 groups: control group, 5-FU group, Avastin group, and combination treatment group. Forty-two days after treatment, tumor weight, inhibition rates, intratumoral microvessel density, apoptosis index, and presence of metastasis were evaluated.

Results: Combination therapy with 5-FU and Avastin augmented the reduction of primary tumor growth and inhibited metastasis compared with treatment with either agent alone. After treatment with Avastin plus 5-FU, a significant increase in apoptotic tumor cells and a decrease in microvessel density were observed.

Conclusions: Avastin plus 5-FU can induce apoptosis in gastric cancer cells and has strong inhibitory effects on tumor growth and the metastasis to the liver. Anti-VEGF therapy in combination with traditional chemotherapy may be a novel therapeutic approach for advanced gastric cancer.