Effect of angiogenesis inhibitor SU6668 on the growth and metastasis of gastric cancer in SCID mice

Abstract

To study the effect of angiogenesis inhibitor SU6668 on the growth and metastasis of gastric cancer in SCID mice. Metastatic model was established by orthotopic implantation of histologically intact human tumor tissue into the gastric wall of SCID mice. Forty-eight mice were randomly divided into four groups, and saline, 5-FU, SU6668, and 5-FU plus SU6668 were administered by i.p. every day for 6 weeks after tumor implantation. The mice were killed and tumor weight, tumor inhibition rate, intratumoral microvessel density(MVD), apoptotic index(AI) and metastasis inhibition were evaluated. Compared with the control, tumor growth was significantly inhibited in mice treated respectively with 5-FU, SU6668 and 5-FU plus SU6668 with inhibition rates of 47.5%, 64.1% and 69.2% respectively. Decreased MVD and increased AI were noted in the mice treated with SU6668 and 5-FU plus SU6668. The incidences of liver and peritoneal metastases was significantly inhibited and decreased to 62.5%, 69.9% in SU6668 group, and 74.9%, 90% in 5-FU plus SU6668 group. The growth and metastasis of human gastric cancer implanted in SCID mice were significantly inhibited in SU6668 group and combined group, especially in combined group. Angiogenesis inhibitor SU6668 has a strong inhibitory effect on tumor growth and metastasis of human gastric cancer transplanted in SCID mice, and has synergistic effect combined with cytotoxic agents.