NRP-1单抗联合节律化疗对裸鼠胃癌移植瘤生长的抑制

Abstract

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[ (0.3940.128)vs(0.7480.152)、(0.8670.361)、(1.2470.494) g;(0.6130.223); vs (0.8660.115)、(1.0980.343)、(1.4740.644); 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; (0.6130.223 vs 0.8660.115, 1.0980.343, 1.4740.644 V/cm~3; P<0.05) and; weight (0.3940.128 vs 0.748 0.152, 0.8670.361, 1.2470.494 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 significantly 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.