EXPERIMENTAL STUDY OF THE EFFECT OF ANGIOGENESIS INHIBITOR TNP-470 ON THE GROWTH AND METASTASIS OF GASTRIC CANCER IN VIVO

Objective: TO study the effect of angiogenesisinhibitor TNP-470 on the growth and metastasis ofgastric cancer in vivo. Methods: Metastatic modelsimulating human gastric cancer was established byorthotopic implantation of histologically intact tumortissue into gastric wall of nude mice. TNP-470 wasadministrated S.C. at doses of 0 mg/kg, 15 mglkg, 30mglkg, 60 mg/kg every other day for eight weeks. Tenweeks after implantation, the mice were sacrificed andthe tumor size measured and the presence of metastasisrecorded. The microvascular density was examined byimmunohistochemical staining with anti-human factorVlll antibody. Results: Compared to the untreatedcontrols, growth of the orthotopically implanted tumorwas significantly reduced in size in the mice treated withTNP-470 with an inhibition rate of 59.9%, 77.0% and84.9% at the dosage of 15 mg/kg, 30 mg/kg and 60 mg/kg,respectively. armor metastasis to the liver andperitoneum was also significantly inhibited in a dosedependent manneL The microvascular density was alsodecreased significantly in the treated mice. Conclusion:Angiogenesis inhibitor TNP-470 has strong inhibitoryeffect both on tumor growth and metastasis of humangastric cancer in nude mice.