Abstract
To study the effect of angiogenesis inhibitor TNP-470 on the growth and metastasis of gastric cancer in vivo. Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice. TNP-470 was administered s.c. at doses of 0 mg/kg, 15 mg/kg, 30 mg/kg, 60 mg/kg every other day for eight weeks. Ten weeks after implantation, the mice were sacrificed and the tumor size measured and the presence of metastasis recorded. The microvascular density was examined by immunohistochemical staining with anti-human factor VIII antibody. Compared to the untreated controls, growth of the orthotopically implanted tumor was significantly reduced in size in mice treated with TNP-470 with an inhibition rate of 59.9%, 77. 0% and 84.9% at the dosage of 15 mg/kg, 30 mg/kg and 60 mg/kg, respectively. Tumor metastasis to the liver and peritoneaum was also significantly inhibited in a dose-dependent manner. The microvascular density was also decreased significantly in the treated mice. Angiogenesis inhibitor TNP-470 has strong inhibitory effect both on tumor growth and metastasis of human gastric cancer in nude mice.
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