PD-L1抑制剂治疗非小细胞肺癌小鼠及对血清IL-4、IFN-γ及生存分析

PD-L1 Inhibitors in the Treatment of Non-Small Cell Lung Cancer Mice and the Analysis of Serum IL-4, IFN-γ and Survival

目的:研究PD-L1抑制剂(阿特朱单抗)治疗非小细胞肺癌小鼠的效果及对血清IL-4、INF-γ水平和小鼠生存时间的影响.方法:将40只615-SCID健康小鼠随机分为4组,每组10只,模型组、PD-L1抑制剂低剂量组,PD-L1抑制剂高剂量组小鼠接种A549细胞,构建非小细胞肺癌小鼠模型.PD-L1抑制剂低剂量组用药,静脉注射阿特朱单抗(1mg/kg,溶于0.1mL生理盐水),PD-L1抑制剂高剂量组用药,静脉注射阿特朱单抗(2mg/kg,溶于0.1mL生理盐水),正常组和模型组给予同等剂量生理盐水.采用ELISA法检测各组小鼠24天后血清IL-4、IFN-γ的表达水平,并观察各组小鼠生存时间.结果:模型组小鼠血清IL-4、INF-γ浓度相比正常组降低,使用PD-L1抑制剂治疗后,低剂量组、高剂量组与模型组相比小鼠血清IL-4、INF-γ浓度均有不同程度升高,且高剂量组上升幅度高于低剂量组,差异显著;模型组肿瘤组织体积增长最快,低剂量组次之,高剂量组最慢,差异显著;模型组最早出现死亡个体,而且最早全部死亡,与模型组相比,高剂量组小鼠生存时间最长,低剂量组略短,差异有统计学意义.结论:PD-L1抑制剂治疗非小细胞肺癌小鼠后,可升高小鼠血清的IL-4、IFN-γ水平,增强免疫功能,延长生存时间.

Objective To study the effect of PD-L1 inhibitor(Atezolizumab)on non-small cell lung cancer in mice and its effects on serum levels of IL-4,INF-γand survival time of mice.Methods A total of 40 615-SCID healthy mice were randomly divided into 4 groups,10 mice in each group.The mice in the model group,and the inhibitor of PD-L1 low dose group and the high dose group were inoculated with A549 cells to construct a mouse model of non-small cell lung cancer.The PD-L1 inhibitors low dose medication,single intravenous injection of Atezolizumab(1mg/kg,dissolved in 0.1mL saline),PD-L1 inhibitors with high dose medication,single intravenous injection of Atezolizumab(2mg/kg,dissolved in 0.1mL saline),normal group and model group were given the same dose of saline.The expression levels of serum IL-4 and INF-γin each group were detected by ELISA method after 24 days,and the survival time of mice in each group was observed.Results Decrease in serum of model group IL-4 and INF-γconcentration compared with the normal group,the use of the PD-L1 inhibitors after treatment,low dose group and high dose group compared with model group,serum IL-4,INF-γconcentration increased,and the high dose group increased significantly higher than the low dose group,significant difference;model group tumor volume growth is the fastest,the low dose group,high dose group is the slowest,significant difference;model group appeared the earliest and most early deaths,all died,compared with the model group,high dose group,the longest survival time of mice,the low dose group is slightly shorter,the difference was statistically significant.Conclusion After treatment with PD-L1 inhibitors,mice with non-small cell lung cancer can increase the levels of IL-4 and IFN-gamma in serum,enhance immune function and prolong survival time.