华蟾素对肺癌大鼠PI3K/AKT信号通路的抑制作用

Inhibitory Effect of Cinobufotalin on Lung Cancer Rats PI3K/AKT Signaling Pathway

关键词:  肺癌  华蟾素  肿瘤标志物  免疫功能  PI3K/AKT信号通路

Key words:  lung cancer  cinobufotalin  tumor markers  immune function  PI3K/AKT signaling pathway

摘要:

目的 探讨华蟾素对肺癌模型大鼠肿瘤标志物、免疫功能及PI3K/AKT信号通路蛋白表达的影响。方法 将80只Wistar大鼠随机分为对照组、模型组、华蟾素组和环磷酰胺组，每组20只，采用气管内灌注致癌碘油液建立肺癌大鼠模型。分别于第4，8周比较组织病理形态、血清肿瘤标志物癌胚抗原（CEA）、糖类抗原-125（CA125）和神经元特异性烯醇化酶（NSE）水平，T细胞亚群CD3⁺、CD4⁺、CD8⁺细胞及NKT细胞含量，AKT-1、Cyclin D1、NF-κB mRNA表达，PI3K、p-AKT蛋白表达。结果 华蟾素组大鼠体质量先减少，3周后逐渐增加，环磷酰胺组大鼠的体质量先减少，4周后有所增加。与模型组比较，华蟾素组和环磷酰胺组的肿瘤体积、质量显著降低，抑瘤率显著增加（P<0.05）；肺组织肿胀不明显，肺泡囊及上皮细胞结构基本清晰；华蟾素组和环磷酰胺组血清CEA、CA125、NSE水平显著降低，AKT-1、Cyclin D1和NF-κB mRNA表达显著降低，PI3K、p-AKT蛋白表达显著降低；华蟾素组CD3⁺和CD4⁺细胞含量显著升高，CD8⁺和NKT细胞含量显著降低，且第8周与第4周相比，差异具有统计学意义（P<0.05）。结论 华蟾素可增加肺癌模型大鼠体质量，降低肿瘤体积和质量，增加抑瘤率，改善肿瘤标志物和免疫功能，其机制可能与降低AKT-1、Cyclin D1、NF-κB mRNA水平和PI3K、p-AKT蛋白表达有关。

Abstract:

OBJECTIVE To investigate the effects of cinobufotalin on the tumor markers, immune function and expression of PI3K/AKT signaling pathway protein in lung cancer model rats. METHODS Eighty Wistar rats were randomly divided into control group, model group, cinobufagin group and cyclophosphamide group, 20 rats in each group. Lung cancer rat model were established by injected with carcinogenic iodized oil solution. The histopathological morphology, serum levels of carcinoembryonic antigen(CEA), carbohydrate antigen-125(CA125) and neuron-specific enolase(NSE), content of CD3⁺, CD4⁺, CD8⁺ and NKT cells, expressions of AKT-1, Cyclin D1, NF-κB mRNA, PI3K and p-AKT proteins were compared at the 4th and 8th weeks respectively. RESULTS The body weight of rats in cinobufotalin group decreased at first, then increased gradually after 3 weeks, and cyclophosphamide group decreased at first, and increased after 4 weeks. The volume and weight of tumors in cinobufotalin group and cyclophosphamide group were decreased significantly, and the inhibition rate were increased significantly(P<0.05). The swelling of lung tissue was not obvious, and pathology obviously and the structure of alveolar sac and epithelial cells was basically clear in cinobufotalin group and cyclophosphamide group. The serum CEA, CA125 and NSE levels in cinobufotalin group and cyclophosphamide group were significantly reduce, the content of CD3⁺, CD4⁺ were increased significantly, the content of CD8⁺ and NKT cells were lower, the expression of AKT-1, Cyclin D1, NF-κB mRNA were significantly reduce, the expression of PI3K and p-AKT protein were significantly reduce, and the 8th week was better than that of the 4th week(P<0.05). CONCLUSION Cinobufotalin can increase the body weight, decrease the volume and weight of lung cancer, increase the inhibition rate, improve the tumor markers and immune function of lung cancer model rats. The mechanism may be related to the decrease of AKT-1, Cyclin D1, NF-κB mRNA level and PI3K, p-AKT protein expression.