Combination therapy with cell-binding domain, angiogenesis inhibitor and Ca2+ channel blocker in mice metastatic model

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Background: In order to prevent tumor metastasis, we investigated more effective inhibition by combination therapy. The competition with native adhesion molecules by cell-binding domain, inhibition of neovascularization with angiogenesis inhibitor TNP-470, and intracellular regulation of store-operated Ca2+ entry by Ca2+ channel blocker.Methods: The cell-binding domain obtained from fibronectin included the Arg-Gly-Asp (RGD) sequence. Tumor metastasis model was created by injecting colon 26/TC-1 cells to CDF1 mice. A fibronectin- binding domain (FND)-treated group, an FND plus TNP-470 group, an FND plus Ca2+ channel blocker (nilvadipine) group, and a control group were established.The mice were sacrificed 4 weeks later and their livers were excised to count the metastatic tumor nodules. And the other study, the mice were not sacrificed and their survival was observed. Results: The mean number of nodules in the FND plus TNP-470 group was significantly smaller than in the control group (P=0.019337), and FND and nilvadipine was significantly smaller than the control group (P< 0.05). The inhibition rate was 51% in the FND group, 64% in the FND (10g) and TNP-470 (100 mg/kg) group, 56% in the inhibition rate in the FND (10g) and nilvadipine (100g) group. The combined effect of FND (10g) and TNP-470 (100 mg/kg) was greater than other treatment. In the survival, all mice died after 4-6 weeks in the control group, the FND plus nilvadipine group mice died after 8-2 weeks.Conclusions: Combination therapy blocks different steps in the process of metastasis may be effective treatment with the non-cytotoxic agents.

Combination therapy with cell-binding domain, angiogenesis inhibitor and Ca2+ channel blocker in mice metastatic model

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