Objective: To study the effects of angiogenesis inhibitor endostatin on the growth and metastasis of gastric cancer in vivo.
Methods: Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice. Endostatin was administered sc at dose of 0 mg/kg, 2.5 mg/kg, 10.0 mg/kg and 20.0 mg/kg every other day for seven weeks. Eight weeks after implantation, the tumor size and inhibition rates and intratumoral microvessel density (MVD) and apoptotic index (AI) and the presence of metastasis are evaluated respectively after the mice were sacrificed.
Results: Compared with the untreated controls, growth of the orthotopically implanted tumor was significantly reduced in size in mice treated with endostatin with an inhibition rate 0, 62.7%, 95.8% and 99.9% at the dosage of 0 mg/kg, 2.5 mg/kg, 10.0 mg/kg, and 20.0 mg/kg, respectively. The MVD was also decreased significantly in the treated mice [(13.7 +/- 3.90) versus (5.73 +/- 2.36), (2.17 +/- 1.28) and (0.66 +/- 0.25)]. The AI was increased significantly in the treated mice [(3.91 +/- 2.58)%, versus (6.76 +/- 5.03)%, (18.92 +/- 6.75)% and (28.57 +/- 10.34)%]. The incidences of peritoneal metastases was also significantly inhibited in the treated mice (87.1% versus 54.5%, 16.7% and 0). The incidences of liver metastases was also significantly inhibited in the treated mice (83.9% versus 27.3%, 8.3% and 0). The growth and metastasis of human gastric cancer implanted in nude mice were significantly inhibited in a dose-dependent manner (P < 0.05).
Conclusions: Angiogenesis inhibitor endostatin can induce apoptosis in gastric cancer by inhibiting tumor angiogenesis and has strong inhibitory effect both on tumor growth and metastasis of human gastric cancer implanted in nude mice.