TrxR抑制剂AA1激活抗肿瘤免疫抑制胃癌进展的实验研究

Experimental study on activation of anti-tumor immunosuppressive gastric cancer by TrxR inhibitor AA1

目的:探究TrxR抑制剂AA1激活抗肿瘤免疫抑制胃癌进展的作用及机制。方法:构建C57BL/6J荷瘤小鼠模型,给予TrxR抑制剂AA1治疗为AA1组,给予PBS为对照组。分别测量不同时间点肿瘤体积,末次给药后观察肿瘤形态与质量;采用ELISA法检测外周血中MDA、SOD含量,流式细胞术检测外周血CD4^(+)、CD8^(+)、NK细胞水平,Western blot检测肿瘤组织中JNK及p-JNK表达。结果:与对照组相比,AA1组小鼠肿瘤体积明显减小(P<0.05),肿瘤质量显著降低,MDA含量明显降低,SOD含量明显升高,外周血CD4^(+)、NK细胞数显著增多,而CD8^(+)细胞数显著减少(P<0.05),2组小鼠肿瘤组织中JNK蛋白表达差异无统计学意义(P>0.05),但AA1组小鼠p-JNK表达显著高于对照组(P<0.05)。结论:TrxR抑制剂AA1可激活荷瘤小鼠免疫功能,增强其机体抗氧化能力,提高JNK信号通路蛋白磷酸化水平,从而抑制其胃癌进展。

Objective:To investigate effect and mechanism of TrxR inhibitor AA1 on anti-tumor immunosuppressive gastric cancer.Methods:C57 BL/6 J tumor-bearing mouse model was established. TrxR inhibitor AA1 was used as AA1 group and PBS was regarded as control group. Tumor volume was measured at different time points,and tumor morphology and quality were observed and compared after last administration. Contents of MDA and SOD in peripheral blood were detected by ELISA,and levels of CD4^(+),CD8^(+),NK cells in peripheral blood were detected by flow cytometry. Western blot to detect JNK and p-JNK proteins levels in tumor tissue.Results:Compared with control group,tumor volume of AA1 group was significantly reduced(P<0.05),and tumor weight was significantly decreased,content of MDA was significantly decreased,content of SOD was significantly increased,number of CD4^(+)and NK cells in peripheral blood was significantly increased,number of CD8^(+)cells was significantly reduced(P<0.05). There was no significant difference in JNK protein expression between two groups(P>0.05),but expression of p-JNK in AA1 group was significantly higher than that in control group(P<0.05).Conclusion:TrxR inhibitor AA1 can activate immune function of tumor-bearing mice,enhance antioxidant capacity and increase phosphorylation level of JNK signaling pathway protein,thus inhibit progress of gastric cancer.