AZD4547联合LAG-3抗体对小鼠肺癌模型的作用

Effect of AZD4547 Combined with LAG-3 Antibody on Mouse Lung Cancer Model

目的探讨成纤维细胞生长因子受体(fibroblast growth factor receptor,rFGFR)抑制剂与淋巴细胞激活基因-3(lymphocyte-activation gene 3,LAG-3)抗体联合应用在非小细胞肺癌小鼠模型中的抗肿瘤效应。方法向6~8周龄的C56BL/6小鼠接种LL2鼠细胞,构建非小细胞肺癌皮下瘤模型,并根据是否给予FGFR抑制剂(AZD4547)与LAG-3抗体分为A组(空白对照)、B组(AZD4547)、C组(LAG-3抗体)和D组(AZD4547联合LAG-3抗体)。接种皮下瘤7天后开始规律给药并测量皮下瘤直径,19天后处死小鼠并剥离皮下瘤,通过免疫组织化学染色和流式细胞术检测肿瘤微环境的特征。结果D组小鼠的皮下瘤较其他3组显著缩小,CD8^(+)T细胞、肿瘤坏死因子-α、白细胞介素-2表达水平升高,差异有统计学意义(P<0.05)。结论联合应用FGFR抑制剂与LAG-3抗体在小鼠皮下瘤模型中显著激活CD8^(+)T细胞,抗肿瘤效应优于单独给药。

Objective To investigate the anti-tumor effect of the combination of FGFR inhibitor AZD4547 and LAG-3 antibody in non-small cell lung cancer mouse models.Methods 6-8 weeks old C56BL/6 mice were inoculated with LL2 mouse cells to construct a subcutaneous tumor model of non-small cell lung cancer.According to whether AZD4547 or LAG-3 antibody were given,mice were divided into four groups,which were group A(blank control),group B(AZD4547),group C(LAG-3 antibody)and group D(AZD4547 combined with LAG-3 antibody).Drugs were administered regularly,and the size of tumor was measured 7 days after inoculation.The mice were sacrificed 19 days after inoculation,and then tumor tissues were taken out.Immunohistochemical staining and flow cytometry were performed to depict the characteristics of immune microenvironment within tumors.Results Compared with the other three groups,the subcutaneous tumors of the mice in the combination group were significantly decreased,while expression levels of CD8^(+)T cells,tumor necrosis factor-α,interleukin-2 increased(P<0.05).Conclusion Combination of AZD4547 and LAG-3 antibody activates CD8^(+)T cells most in the mouse subcutaneous tumor model,and the anti-tumor effect is better than that of single drug administration.