CDA-2抑制肺癌生长的炎症机制研究

Inhibitive effect of cell differentiation agent 2（CDA-2） on lung cancer in mice and its mechanism

关键词:  肺肿瘤  CDA-2  NF-κB  小鼠

Key words:  lung tumor  CDA-2  NF-κB  mouse

摘要:

目的探究尿多酸肽（CDA-2）抑制肺癌生长的作用及炎症机制。方法通过给雌性C57BL/6小鼠尾静脉注射LLC细胞,建立小鼠肺癌模型。采用肿瘤计数和测量大小评价CDA-2对肺肿瘤增殖的影响;收集经CDA-2治疗过的小鼠肺支气管肺泡灌洗液（BALF）并分离肺泡巨噬细胞,采用白细胞分类计数、电泳迁移位移试验（EMSA）、ELISA试验,研究CDA-2抑制肿瘤的作用机制。结果与对照相比,CDA-2明显抑制小鼠肺肿瘤的生长,肿瘤数和肿瘤尺寸显著下降（P〈0.05）。经CDA-2处理后支气管肺泡灌洗液（BALF）的巨噬细胞中的NF-κB与靶DNA结合的活性被强烈的抑制。此外,CDA-2处理显著减少BALF中各种炎性细胞的数量（P〈0.05）,以及炎症因子TNFα,IL-6,KC在肺组织中的表达（P〈0.05）。结论 CDA-2能抑制肺肿瘤的生长,通过抑制髓系细胞中NF-κB的活性,减少肺部炎症,可能是CDA-2抑制肺癌的生长的机制。

Abstract:

Objective To investigate the effect of cell differentiation agent 2（ CDA-2） on lung cancer and its mechanism. Methods The lung cancer model was induced by intravenous injection of LLC cells in C57 BL /6 mice. CDA-2 2 000 mg / kg or same volume of PBS（ in control group） was injected intraperitoneally in cancer-bearing mice. The number and size of tumor were measured. The alveolar macrophages in bronchoalveolar lavage fluid（ BALF） were collected and counted.Macrophage to target NF-κB DNA binding activity was determined by electrophoretic mobility shift assay（ EMSA）,and TNFα,IL-6 and KC were measured by enzyme linked immunosorbent assay（ ELISA）. Results Compared with the control group,CDA-2 treatment inhibited tumor number and size significantly（ P〈0. 05）. Macrophages to target NF-κB DNA binding activity was strongly suppressed after CDA-2 treatment. CDA-2 treatment significantly reduced the number of inflammatory cells in BALF（ P〈0. 05）, and contents of TNFα, IL-6, KC（ P〈0. 05） in lung tissue.Conclusion CDA-2 can inhibit lung tumor development,which may be associated with the reduction of inflammation in lung tissue through suppression of NF-κB activation.