NRP-1单抗联合节律化疗对裸鼠胃癌移植瘤生长的抑制

NRP-1 monoclonal antibody in combination with metronomic chemotherapy(MCT) inhibits the growth of gastric cancer xenografts in nude mice

目的:探讨NRP-1单抗联合多西他赛节律化疗对胃癌裸鼠移植瘤的抗肿瘤疗效。方法:BALB/c裸鼠皮下接种胃癌BGC-823细胞制备移植瘤模型,将荷瘤裸鼠以数字随机表法随机分为对照组、NRP-1单抗组、节律化疗组(MCT)、联合组(NRP-1mAb+MCT),每组6只。除对照组,其余各组于造模第8天开始分别给予相应治疗,给药2周,观察裸鼠一般状况,隔天测量裸鼠体重及肿瘤体积。裸鼠处死后称瘤质量,H-E染色观察瘤组织形态,免疫组化检测裸鼠瘤组织中NRP-1蛋白、VEGF、MVD表达。结果:联合组移植瘤的体积和质量显著低于其他各组[(0.394±0.128)vs(0.748±0.152)、(0.867±0.361)、(1.247±0.494)g;(0.613±0.223)vs(0.866±0.115)、(1.098±0.343)、(1.474±0.644)cm^3。均P<0.05],抑瘤率较其他治疗组差异有统计学意义(P<0.05)。对照组癌组织细胞生长良好,血管丰富,给药组癌组织出现不同程度的片状坏死,血管成分减少。免疫组化染色显示,对照组NRP-1表达明显高于治疗各组(P<0.05),联合组的NRP-1、VEGF、MVD表达均显著低于其余各组(P<0.05)。结论:NRP-1单抗联合多西他赛节律化疗可能通过下调NRP-1表达而显著抑制BGC-823胃癌移植瘤的生长及血管生成。

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.