PD-1单抗联合顺铂或吉西他滨化疗对KRAS突变非小细胞肺癌A549细胞移植瘤小鼠模型的治疗作用OA北大核心CSTPCD

Objective:To investigate the therapeutic effect of programmed death-1 monoclonal antibody(PD-1 mAb)combined with cisplatin and gemcitabine in the treatment of transplanted tumor with KRAS gene mutant non-small cell lung cancer(NSCLC)A549 cells in mice.Methods:By constructing an immune system-tumor humanized mouse xenograft model with NSCLC A549 cells,60 mice were randomly divided into 6 groups(10 mice/group),namely control group(200 μL/kg PBS),PD-1 mAb group(20 mg/kg PD-1 mAb),cisplatin group(3 mg/kg cisplatin),PD-1 mAb+cisplatin group(20 mg/kg PD-1 mAb+3 mg/kg cisplatin),gemcitabine group(30 mg/kg gemcitabine)and PD-1 mAb+gemcitabine group(20 mg/kg PD-1 mAb+30 mg/kg gemcitabine).TUNEL and DAPI double staining were used to detect the level of apoptosis in transplanted tumor tissues.The volume and mass of transplanted tumors were detected,and the growth inhibition rate of transplanted tumor was measured.The microvessel density(MVD)of transplanted tumor was determined by immunohistochemistry.Results:The humanized mouse xenograft model of NSCLC A549 cells was successfully constructed.Compared with the other five groups,the apoptosis rate and tumor growth inhibition rate in the PD-1 mAb+cisplatin group were the highest,and the tumor volume,mass,and MVD were the smallest(all P<0.05).Conclusion:Cisplatin has a synergistic activity with PD-1 mAb,while gemcitabine can antagonize the therapeutic effect of PD-1 mAb.It is suggested that PD-1 mAb combined with cisplatin chemotherapy is better for KRAS mutant NSCLC A549 cell transplanted tumor mice.