Inhibitory Effect of TNP-470 on Lymph Node Metastasis of Human Gastric Carcinoma Line Established by Orthotopic Implantation

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We assessed the anti-tumor and antimetastatic effects of angiogenic inhibitor TNP-470, 6-O- ( N-chloroacetyl-carbamoyl ) -fumagillol, semisynthtic analogue of fumagillin, on lymph node metastasis of human gastric carcinoma using our established orthotopic implantation model of AZL5G. This line was derived from a parental human gastric cancer cell line, AZ521, which had low capacity for metastasis. 5×106 cells were implanted orthotopically into the stomachs of nude mice, which had been randomly divided into 3 groups: a control group given saline solution, a group receiving 15 mg/kg TNP-470, a group receiving 30 mg/kg TNP-470. TNP-470 (15 or 30 mg/kg) was given s.c. on alternate days for 6 weeks from day 1 after orthotopic implantation. In the control group, lymph node metastasis developed in 5 of 6 mice (83.3%). Lymph node metastasis developed in 3 of 4 mice (75.0%) receiving of 15mg/kg TNP-470, and in 3 of 5 mice (60.0%) receiving of 30mg/kg TNP-470. TNP-470 was revealed to have no inhibitory effect on the incidence of lymph node metastasis. However, it was also observed that administration of 30mg/kg TNP-470 reduced the number of lymph node metastases statistically. The inhibitory effect on the production of vascular endothelial growth factor (VEGF) by AZL5G cells were not altered by TNP-470 administration at the concentration ranging from 10-1 to 103 ng/ml. These results indicate that administration of TNP-470 in co-administration cytotoxic agents may be effective on keeping micrometastases dormant in the clinical therapeutic strategy for gastric cancer patients.
札幌医科大学の論文

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