基于IL-17/NF-κB信号通路探讨敦煌医方大补脾汤联合奥沙利铂对胃癌荷瘤小鼠炎症免疫的影响

Effect of Dunhuang medical prescription Dabupi Decoction combined with oxaliplatin on inflammatory immunity of gastric cancer-bearing mice based on IL-17/NF-κB signaling pathway

目的:研究敦煌医方大补脾汤对胃癌荷瘤小鼠的抑瘤作用以及基于IL-17/NF-κB信号通路探讨大补脾汤联合奥沙利铂对胃癌荷瘤小鼠炎症免疫的影响。方法:建立MFC胃癌皮下荷瘤小鼠模型,随机分为模型组、奥沙利铂组、大补脾汤高、中、低剂量联合奥沙利铂组[21.58、10.79、5.40 g/(kg·d)],每组10只,雌雄分笼饲养,接种8 d后开始给药,连续给药14 d;末次给药后次日眼球取血,处死小鼠,摘取肿瘤组织称重,计算抑瘤率;ELISA检测小鼠血清IL-17和IL-6含量,免疫组化(IHC)、RT-qPCR和Western blot分别检测小鼠肿瘤组织IL-17、IL-6、NF-κB和pNF-κB mRNA和蛋白表达。结果:奥沙利铂组、大补脾汤高、中、低剂量联合奥沙利铂组抑瘤率分别为33.02%、52.92%、46.33%和39.52%,各给药组肿瘤质量均较模型组显著降低(P<0.01),大补脾汤高、中、低剂量联合奥沙利铂组显著高于奥沙利铂组(P<0.01);与模型组相比,各给药组血清IL-17和IL-6含量、肿瘤组织IL-17、IL-6、NF-κB p65和pNF-κB p65 mRNA和蛋白表达显著降低(P<0.01,P<0.05);与奥沙利铂组相比,大补脾汤高、中剂量联合奥沙利铂组血清IL-17和IL-6含量、肿瘤组织IL-17、IL-6、NF-κB p65和pNF-κB p65 mRNA和蛋白表达显著降低(P<0.01,P<0.05)。结论:敦煌医方大补脾汤对MFC胃癌荷瘤小鼠具有一定抑瘤作用,并可通过抑制IL-17/NF-κB信号通路调控炎症免疫,抑制胃癌发生发展。

Objective:To study anti-tumor effect of Dunhuang medical prescription Dabupi Decoction on gastric cancer-bearing mice and effect of Dabupi Decoction combined with oxaliplatin on inflammatory immunity of gastric cancer-bearing mice based on IL-17/NF-κB signaling pathway.Methods:Mouse model of MFC gastric cancer subcutaneously bearing tumor was established and ran-domly divided into model group,oxaliplatin group,high,medium and low doses of Dabupi Decoction combined with oxaliplatin groups[21.58,10.79,5.40 g/(kg·d)],with 10 mice in each group,male and female cage rearing.Administration began after 8 days of inoculation and continued for 14 days;next day after the last administration,eyeball blood was taken,mice were killed,tumor tissues were taken and weighed,and tumor inhibition rate was calculated.ELISA was used to detect contents of IL-17 and IL-6 in mice serum,immunohistochemistry(IHC),RT-qPCR and Western blot were used to detect IL-17,IL-6,NF-κB and p-NF-κB mRNA and protein expressions in mice tumor tissues,respectively.Results:Tumor inhibition rates of oxaliplatin group,high,medium and low doses of Dabupi decoction combined with oxaliplatin groups were 33.02%,52.92%,46.33%and 39.52%,respectively,and tumor quality of each treatment group was significantly lower than that of model group(P<0.01).High,medium and low doses of Dabupi Decoction combined with oxaliplatin groups were higher than that of oxaliplatin group.Compared with model group,contents of IL-17 and IL-6 in serum and expressions of IL-17,IL-6,NF-κB p65 and pNF-κB p65 mRNA and protein in tumor tissues in each treatment group were significantly reduced(P<0.01,P<0.05).Compared with oxaliplatin group,levels of IL-17 and IL-6 in serum and expres-sions of IL-17,IL-6,NF-κB p65 and pNF-κB p65 mRNA and protein in tumor tissues in high and medium doses of Dabupi Decoction combined with oxaliplatin groups were significantly reduced(P<0.01,P<0.05).Conclusion:Dunhuang medical prescription Dabupi Decoction has a certain anti-tumor effect on MFC gastric cancer-bearing mice,which can regulate inflammatory immunity and inhibit occurrence and development of gastric cancer by inhibiting IL-17/NF-κB signaling pathway.