Effect of SU5416 on the inhibition of growth and metastasis of human gastric cancer implanted in nude mice

Abstract

OBJECTIVE:  To study the effects of the angio­genesis inhibitor SU5416 on the growth and liver metastasis of gastric cancer and to investigate its effects on the apoptosis of gastric cancer cells. METHODS:  A model simulating the metastasis of human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into the gastric wall of nude mice, which were randomly divided into four groups: control group (saline solution), 5-FU group (fluorouracil 30 mg/kg per day i.p), SU5416 group (SU5416 15 mg/kg per day i.p.), and combined treatment with 5-Fu and SU5416. Eight weeks after implantation, the tumor weight, inhibition rate, intratumoral microvessel density (MVD), apoptotic index (AI), and the status of metastasis were evaluated after the mice were killed. RESULTS:  Compared with the control group, the growth of the orthotopically-implanted tumors was significantly inhibited, with reduced weight, and the tumor inhibition rate was 44.5%, 79.3%, and 84.4%, respectively, in the mice treated with 5-FU, SU5416 and both. The incidence of liver metastasis was also significantly decreased in the 5-Fu, SU5416, and combination groups compared with the control group (36.4%, 25.0%, and 0% vs 90.0%). The MVD of the 5-FU group, the SU5416 group and the combined group was 13.1 ± 4.7, 3.9 ± 1.8 and 2.1 ± 1.5, respectively, which was decreased significantly compared with the control group (14.6 ± 5.8). The AI was increased significantly in the treated mice (6.81 ± 4.92%, 9.82 ± 3.76% and 17.65 ± 9.85% vs 3.76 ± 2.25%). The growth of and liver metastasis of the human gastric cancer implanted in the nude mice were both more significantly inhibited in the SU5416 group and the combined group than in the control and 5-FU groups (P < 0.05). CONCLUSIONS:  SU5416 can induce apoptosis in gastric cancer by inhibiting tumor angiogenesis and has a strong inhibitory effect on both the growth and liver metastasis of gastric cancer implanted in nude mice. The combination of SU5416 with other cytotoxic agents is more effective.