NRP- 1 monoclonal antibody in combination with metronomic chemotherapy(MCT) inhibits the growth of gastric cancer xenografts in nude mice
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Abstract:
Objective: To investigate the antitumor effect of NRP-1 monoclonal antibody combined with docetaxel metronomic chemotherapy in nude mice bearing gastric cancer xenografts. Methods: BALB / c mice were inoculated subcutaneously with BGC-823 cells to establish xenograft model; the tumor bearing rats were randomly divided into control group, NRP-1 monoclonal antibody group (NRP-1mAb), rhythm chemotherapy group (MCT) and combined group (NRP-1mAb+MCT). Except the control group, the other three groups were given the corresponding treatment on the 8th day after the model establishment. After 2 weeks of administration, the general condition of nude mice was observed and the body weight and tumor volume were measured the next day. The mice were sacrificed and the mass of tumor was calculated; HE staining was used to observe the morphology of the tumor tissue.The expression of NRP-1 protein, VEGF and MVD were detected by immunohistochemistry. Results: The tumor volume (0.613±0.223 vs 0.866±0.115, 1.098±0.343, 1.474±0.644 V/cm3; P<0.05) and weight (0.394±0.128 vs 0.748±0.152, 0.867±0.361, 1.247±0.494 m/g; P<0.05) of the combined group were significantly lower than those of the other groups, and the tumor inhibition rate was statistically higher compared with the other treatment groups (P<0.05). Under microscope, the cancer cells in the control group were well grown and the blood vessels were rich; the cancerous tissues of each treatment group showed different degree of sheet necrosis and the blood vessel composition decreased. Immunohistochemistry results showed that the expression of NRP-1 in the control group was signifi-cantly higher than that in each treatment group (P<0.05); and the expression of NRP-1, VEGF and MVD in combined treatment group was significantly lower than the other groups. Conclusion: NRP-1 monoclonal antibody combined with docetaxel rhythmic chemotherapy may significantly inhibit the growth and angiogenesis of BGC-823 gastric cancer by down-regulating the expression of NRP-1.