Inhibition of growth and metastasis of implanted human gastric cancer in nude mice by SU5416 / 中华消化杂志

ABSTRACT

Objective To study the effects of angiogenesis inhibitor SU5416 on the growth and metastasis to the liver of gastric cancer and to investigate its effect on the apoptosis of gastric cancer cells. Methods Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice. Mice were randomly divided into 4 groups control group (saline solution), 5 FU group (fluorouracil 30 mg?kg -1 ?d -1 i.p.), SU5416 group (SU5416 15 mg?kg -1 ?d -1 i.p.), and combined treatment of both 5 FU and SU5416 group. Eight weeks after implantation, the tumor weight, inhibition rates, intratumoral microvessel density (MVD), apoptotic index (AI), and the presence of metastasis were evaluated respectively after the mice were sacrificed. Results Compared with the control group, the growth of the orthotopically implanted tumor was significantly inhibited due to the reduced weight and the inhibition rate of tumor was 44.5%, 79.3%, and 84.4% respectively in mice treated with 5 FU, SU5416 and both. The incidences of liver metastases were also significantly decreased in the 5 FU group, SU5416 group, and combined group compared with those in control group (36.4%, 25.0%, and 0% vs 90.0%). The MVD was decreased significantly in the treated mice ( 14.6 ? 5.8 vs 13.1?4.7, 3.9? 1.8 , and 2.1?1.5). The AI was increased significantly in the treated mice [(3.76?2.25)% vs (6.81? 4.92 )%, (9.82?3.76)% and (17.65?9.85)%]. The growth and liver metastasis of human gastric cancer implanted in nude mice were more significantly inhibited in the SU5416 group and combined group than in control group and 5 FU group ( P