PD-L1单克隆抗体联合双歧杆菌对小鼠胃癌的疗效观察

Therapeutic Effect of PD-L1 Monoclonal Antibody Combined with Bifidobacterium on Gastric Cancer in Mice

目的探究人类程序性死亡配体-1(programmed death ligand-1,PD-L1)单克隆抗体联合双歧杆菌对胃癌的疗效。方法选取4周龄BALB/C裸鼠20只,给予自由饮水饮食、SPF级饲养6 w后,进行体内实验,首先采用细胞成瘤实验,应用随机数字表法将其分为SGC7901胃癌细胞皮下成瘤模型组、PD-L1单克隆抗体治疗胃癌模型组、双歧杆菌灌服胃癌模型组、PD-L1单克隆抗体联合双歧杆菌治疗胃癌模型组,21 d后脱颈处死小鼠,取小鼠体内的肿瘤组织,进行称重、计算肿瘤体积;进行鼠肿瘤组织PD-1及PD-L1蛋白及基因的相关检测。结果与PD-L1单克隆抗体及双歧杆菌单独治疗对比,联合应用PD-L1单克隆抗体和双歧杆菌可明显抑制胃癌的增长(P<0.05);Western-blot和qRT-PCR实验结果显示,联合应用后能够降低各组小鼠胃癌组织中的PD-1和PD-L1的表达(P<0.05)。结论PD-L1单克隆抗体和双歧杆菌的联合应用,能够抑制胃癌组织中PD-1/PD-L1的表达,抑制肿瘤的增殖,使肿瘤体积缩小,重量减轻,有较好的疗效,为临床治疗胃癌提供新的思路。

Objective To explore the efficacy of human programmed death ligand-1(PD-L1)monoclonal antibody combined with bifidobacteria on gastric cancer.Methods Twenty four-week-old BALB/C nude mice were selected and fed with a free-drinking diet and SPF-grade rearing for 6 weeks.The in vivo experiment was carried out.First,the cell tumor formation experiment was used,and the random number table method was used to divide them into SGC7901 gastric cancer cells subcutaneously.Tumor model group,PD-L1 monoclonal antibody treatment gastric cancer model group,bifidobacteria gavage gastric cancer model group,and PD-L1 monoclonal antibody combined with bifidobacteria treatment gastric cancer model group.21 days later,the mice were killed by removing the neck.The tumor tissue was taken out and was weighed.The tumor volume was calculated.The PD-1 and PD-L1 proteins and genes of the mouse tumor tissue were detected.Results Compared with PD-L1 monoclonal antibody and bifidobacteria alone,the combined application of PD-L1 monoclonal antibody and bifidobacteria can significantly inhibit the growth of gastric cancer(P<0.05);Western-blot and qRT-PCR experimental results have shown that the combined application can reduce the expression of PD-1 and PD-L1 in mouse gastric cancer tissues in each group(P<0.05).Conclusion The combined application of PD-L1 monoclonal antibody and bifidobacteria can inhibit the expression of PD-1/PD-L1 in gastric cancer tissues,inhibit tumor proliferation,reduce tumor volume and weight,and has a good curative effect,providing new ideas for the clinical treatment of gastric cancer.