ST2抗体治疗对Kras^(G12D)非小细胞肺癌小鼠肿瘤标志物的水平和IL-33、ST2表达的影响

Effects of ST2 antibody treatment on the expression of tumor markers,IL-33 and ST2 antiboty in Kras^(G12D) mice with non-small cell lung cancer

目的:探讨ST2抗体治疗对Kras^(G12D)小鼠非小细胞肺癌中肿瘤标志物神经烯醇化酶(NSE)、癌胚抗原(CEA)水平和IL-33、ST2表达的影响。方法:以野生型(WT)非小细胞肺癌小鼠为对照组,Kras^(G12D)非小细胞肺癌小鼠为试验组,用ELISA法于第6周、12周、18周检测小鼠血清中NSE和CEA的水平;流式细胞术检测小鼠肺肿瘤组织中的调节性T细胞(Tregs)以及表达ST2抗体的Tregs细胞的比例;RT-qPCR检测小鼠支气管肺泡灌洗液(BALF)和肺组织中IL-33的表达水平。结果:随着周龄增长,Kras^(G12D)小鼠血清中NSE和CEA的水平不断提高,肺肿瘤中Tregs高度表达ST2抗体(P<0.05);ST2抗体治疗可清除Kras^(G12D)小鼠肺癌中活化的Tregs,增强抗肿瘤免疫反应,降低血清NSE、CEA水平(P<0.05)。结论:Tregs中ST2抗体的表达可上调Kras^(G12D)小鼠血清中NSE、CEA的水平,并且ST2抗体治疗可通过清除肺组织中活化的Tregs,减轻肿瘤负担,降低血清中NSE和CEA的水平。

Objective:To investigate the effects of ST2 antibody treatment on the expression of tumor markers neuron-specific enolase(NSE)and carcinoembryonic antigen(CEA),IL-33 and ST2 in Kras^(G12D) mice with non-small cell lung cancer.Methods:Wild-type(WT)mice without non-small-cell lung cancer and Kras^(G12D) mice with non-small-cell lung cancer were selected as the controls and treated groups.The ELISA method was used to detect the levels of NSE and CEA in the mice's serum at 6th week,12th week and 18th week of tumor progression.Also,the proportion of regulatory T cells(Tregss)in the tissue of lung tumor Tregsand those expressing ST2 was evaluated by flow cytometry.Additionally,the expression of IL-33 in bronchoalveolar lavage fluid(BALF)and lung tissue was analyzed through quantitative real-time polymerase chain reaction(qRT-PCR).Results:The levels of NSE and CEA in the serum of Kras^(G12D) mice were increased with age,and ST2 was highly expressed in Tregs of non-small-cell lung tumors were increased(P<0.05).Furthermore,the in vitro introduce of ST2 antibody could clear the activated Tregs in Kras^(G12D) mice with non-small-cell lung cancer,enhance the anti-tumor immune response,and reduce the levels of NSE and CEA in mice's serum(P<0.05).Conclusion:The expression of ST2 in Tregs up-regulate the levels of NSE and CEA levels in Kras^(G12D) mice's serum,while the in vitro introduce of ST2 antibody effectively reduce the burden of tumors and the levels of NSE,CEA by clearing activated Tregs in lung tumors.