顺铂联合VEGF抗体对食管癌移植瘤小鼠免疫调节以及癌细胞增殖和肺转移的影响

摘要 目的：研究顺铂联合血管内皮生长因子（vascular endothelial growth factor，VEGF）治疗对食管癌移植瘤小鼠免疫功能、癌细胞增殖以及肺转移的影响。方法：30只BALB/c小鼠通过皮下注射食管癌移植瘤模型。一周后，30只食管癌移植瘤模型小鼠被随机均分为3组，即模型组、顺铂组和联合组。模型组不进行治疗，顺铂组腹腔注顺铂治疗，联合组腹腔注射顺铂联合尾静脉注射VEGF抗体进行治疗，共治疗7周。比较各组小鼠体重，食管癌移植瘤体积和重量，卵巢癌细胞肺组织转移结节数、癌细胞转移面积和转移病灶总数，以及食管癌移植瘤外周血CD4⁺、CD8⁺以及CD4⁺/CD8⁺ T淋巴细胞比例。结果：（1）顺博组和联合组小鼠体重均显著高于对照组，而联合组小鼠体重显著高于顺铂组（P<0.05）；（2）顺铂组和联合组小鼠CD4+和CD8+细胞比例均显著低于对照组（P<0.05），而CD4⁺/CD8⁺却显著高于对照组（P<0.05）；（3）联合组小鼠CD4⁺和CD8⁺细胞比例均显著高于对照组（P<0.05），而CD4⁺/CD8⁺却显著低于顺铂组（P<0.05）；（4）顺铂组和联合组小鼠食管癌肿瘤组织体积和重量，肺转移结节数、转移面积和转移病灶数均显著低于对照组（P<0.05），而联合组小鼠显著低于顺铂组（P<0.05）。结论：VEGF抗体可以显著增强顺铂在体内对食管癌的抗癌特性，并有助于增强食管癌移植瘤小鼠免疫功能、抑制癌细胞体内增殖和肺部转移。

Effect of Cisplatin Combined with VEGF Antibody on Immune Regulation, Cancer Cell Proliferation and Lung Metastasis in Mice Transplanted with Esophageal Cancer

ABSTRACT Objective: To study the effect of cisplatin combined with vascular endothelial growth factor (VEGF) treatment on the immune function, cancer cell proliferation and lung metastasis of esophageal cancer transplanted mice. Methods: Thirty BALB/c mice were injected subcutaneously into the esophageal cancer xenograft model. One week later, 30 esophageal cancer transplanted tumor model mice were randomly divided into 3 groups, namely model group, cisplatin group and combination group. The model group was not treated, the cisplatin group was treated with intraperitoneal cisplatin, and the combination group was treated with intraperitoneal cisplatin combined with tail vein injection of VEGF antibody for a total of 7 weeks. Compare the body weight of each group of mice, the volume and weight of esophageal cancer transplanted tumor, the number of ovarian cancer cell lung tissue metastatic nodules, the area of cancer cell metastasis and the total number of metastatic lesions, and the peripheral blood CD4⁺, CD8⁺ and CD4⁺/CD8⁺ T lymph of esophageal cancer transplanted tumor Cell ratio. Results: (1) The weight of mice in the cisplatin group and the combination group was significantly higher than that of the control group, while the weight of the mice in the combination group was significantly higher than that in the cisplatin group (P<0.05); (2) CD4⁺ and CD8⁺ cells in the cisplatin group and the combination group The ratios were significantly lower than those of the control group (P<0.05), while the CD4⁺/CD8⁺ ratios were significantly higher than those of the control group (P<0.05); (3) The ratios of CD4⁺ and CD8⁺ cells in the combination group were significantly higher than those of the control group (P<0.05), while CD4⁺/CD8⁺ was significantly lower than that of the cisplatin group (P<0.05); (4) the volume and weight of esophageal cancer tumor tissue, the number of lung metastasis nodules, the area of metastasis, and the metastatic lesions in the cisplatin group and the combination group The numbers were significantly lower than those in the control group (P<0.05), while the mice in the combination group were significantly lower than those in the cisplatin group (P<0.05). Conclusion: VEGF antibody can significantly enhance the anti-cancer properties of cisplatin against esophageal cancer in vivo, and help to enhance the immune function of esophageal cancer transplanted mice, and inhibit the proliferation of cancer cells in vivo and lung metastasis.