摘要
目的 探讨程序性死亡受体 1(PD-1)抑制剂联合艾坦在三阴性乳腺癌(TNBC)小鼠模型中的应答差异.方法 采用 4T1 细胞建立TNBC小鼠模型,32 只成瘤后的小鼠随机分为模型组、PD-1 抑制剂组、艾坦组和联合组,每组各 8 只.记录并计算各组小鼠肿瘤体积和抑瘤率,检测血清及肿瘤细胞中程序性死亡-配体 1(PD-L1)表达情况.结果 造模后 7、14、21、28 d,模型组小鼠瘤体体积明显高于PD-1 抑制剂组、艾坦组和联合组小鼠瘤体体积(P<0.05).模型组小鼠造模后 7~14 d瘤体体积快速增长,其余各组瘤体体积明显受到抑制.联合组小鼠瘤体明显小于PD-1 抑制剂组、艾坦组(P<0.05).造模后 28 d,联合组抑瘤率明显高于PD-1 抑制剂组、艾坦组,差异有统计学意义(P<0.05).PD-1 抑制剂组和联合组血清PD-L1 和肿瘤阳性率明显高于模型组和艾坦组,差异有统计学意义(P<0.05);PD-1 抑制剂组和联合组血清PD-L1 和肿瘤PD-L1 阳性率比较差异无统计学意义(P>0.05).结论 PD-1 抑制剂联合艾坦在TNBC治疗中具有协同抗肿瘤作用,能有效抑制肿瘤生长.
Abstract
Objective To explore the response difference of programmed death receptor 1(PD-1)inhibitor combined with Aitan(Apatinib)in a triple negative breast cancer(TNBC)mouse model.Methods 4T1 cells were used to establish a TNBC mouse model,and 32 mice were randomly divided into the model group,the PD-1 inhibitor group,the Aitan group and the combination treatment group after tumor formation,with 8 mice in each group.The tumor volume and tumor inhibition rate of each group of mice were recorded and calculated,and the expression of programmed death ligand 1(PD-L1)in serum and tumor cells was detected.Results At 7 d,14 d,21 d,and 28 d after modeling,the tumor volume of the model group was significantly higher than that of the PD-1 inhibitor group,Aitan group,and combination treatment group(P<0.05).The tumor volume of the model group increased rapidly 7-14 days after modeling,while the tumor volume of other groups was significantly inhibited.The tumor size of the combination treatment group was significantly smaller than that of the PD-1 inhibitor group and the Aitan group(P<0.05).After 28 days of modeling,the tumor inhibition rate of the combination treatment group was significantly higher than that of the PD-1 inhibitor group and the Aitan group,with statistically significant difference(P<0.05).The serum PD-L1 and tumor positivity rates in the PD-1 inhibitor group and the combination treatment group were significantly higher than those in the model group and the Aitan group,with statistically significant differences(P<0.05).There were no significant differences in the positive rates of serum PD-L1 and tumor PD-L1 between the PD-1 inhibitor group and the combination treatment group(P>0.05).Conclusion The combination of PD-1 inhibitors and Aitan has a synergistic anti-tumor effect in the treatment of TNBC,which can effectively inhibit tumor growth.
基金项目
黑龙江省齐齐哈尔市科技计划联合引导项目(LSFGG-2022009)