PD-1单克隆抗体联合血管内皮抑素在Lewis肺癌小鼠的抗肿瘤效应

Combinatorial anti-PD-1 and endostatin therapeutic efficacy in Lew is lung cancer mice

目的探讨程序性死亡受体-1(PD-1)单克隆抗体联合血管内皮抑素对Lewis肺癌小鼠的抗肿瘤效应。方法构建Lewis肺癌C57BL/6小鼠移植瘤模型,随机分为4个组:PBS对照组(A组)、PD-1单克隆抗体组(B组)、血管内皮抑素组(C组)、PD-1单克隆抗体联合血管内皮抑素组(D组)。测量小鼠肺内肿瘤体积,ELISA检测小鼠血浆中INFγ的含量,免疫组织化学染色检测肿瘤组织的CD31和VEGF。结果与A组相比,B组、D组肿瘤生长受到明显抑制(P均<0.001),C组肿瘤虽有缩小但差异无统计学意义(P=0.084);与A组相比,B、C、D组血浆中INFγ的浓度明显升高(P均<0.001),D组升高最为明显;与A组相比,D组小鼠肿瘤组织中VEGF的阳性表达最低(P<0.001);MVD计数D组降低,与A组相比(P<0.001),D组与B组相比(P=0.019),D组与C组相比(P<0.001)。结论 PD-1单克隆抗体联合血管内皮抑素治疗明显减缓肿瘤生长速度,有效改善肿瘤微环境,有明显协同抗肿瘤作用。

Objective To explore the antitumor effect of anti-PD-1 combined with angioendostatin on lung cancer in Lewis mice. Methods Lewis lung cancer C57 BL/6 mice models were constructed and randomly divided into 4 groups： group A（ PBS control）,group B（ anti-PD-1）,group C（ endostatin） and group D（ anti-PD-1 combined with endostatin）. The tumor volume was measured. The content of INFγ in the plasma was detected with ELISA,and the CD31 and VEGF contents were determined with immunohistochemistry. Results Compared with group A,group B and D had significantly inhibited tumor growth（ P〈0. 001）; group Chad reduced tumor size but there was no statistical difference（ P = 0. 084）. Compared with group A,groups D,C and B had significantly elevated INFγ concentration（P〈0. 001）,and group D showed the most obvious increase. Compared with group A,group D had significantly lower positive expression of VEGF（ P〈0. 001）. MVD count decreased significantly in group D compared with that in group A（ P〈0. 001）,group D compared with group B（ P = 0. 019）,and group D compared with group C（ P〈0.001）. Conclusion Anti-PD-1 combined with endostatin can significantly slowdown the tumor growth,effectively improve the tumor microenvironment,and play a synergistic antitumor effect.