Caveolin-1和Caspase-3在大鼠肺鳞癌形成中的动态表达

Dynamic Expression of Caveolin-1 and Caspase-3 Proteins in the Rat Lung Squamous Cell Cancer Formation

目的:检测窖蛋白-1(Caveolin-1,Cav-1)和半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)在大鼠肺鳞癌形成过程中的蛋白表达并探讨其意义。方法:采用左肺叶支气管灌注含甲基胆蒽的碘油溶液诱发大鼠肺鳞癌,应用免疫组化SP法检测肺鳞癌发生过程中各阶段组织Cav-1、Caspase-3的蛋白表达并计算免疫组化评分(IHS)。提取病变肺组织的蛋白裂解物,Western blot检测不同阶段病变组织的Cav-1蛋白含量。结果:实验组多个阶段病变共存的动物标本有80.00%(64/80),其中获取支气管黏膜上皮增生14例,鳞状化生25例,不典型增生35例,原位癌12例,浸润癌54例,转移癌15例。正常肺组织Cav-1蛋白高表达,增生、鳞化、不典型增生、原位癌阶段Cav-1的IHS下降,与正常肺组织相比差异均有极显著性(P<0.01)。原位癌、浸润癌与转移癌之间Cav-1的IHS逐步增高(P<0.05)。10例对照组大鼠支气管黏膜上皮细胞中8例(80.00%)有Caspase-3的阳性表达,不典型增生、浸润癌和转移癌阶段Caspase-3的IHS逐步降低,差异均有显著性(P<0.05)。在对照组和实验组共165例大鼠肺组织病变中,Cav-1与Caspase-3无明显相关性(r=0.035,P=0.771)。结论:Cav-1在肺癌发生及侵袭转移过程中呈动态表达,与肺癌细胞适应不同的生长需要密切相关。Caspase-3蛋白下降参与了肺癌的发生和发展。

Objective： To investigate the dynamic expression caveolin-1（Cav-1） and Caspase-3 in relation to carcinogenesis,invasion,and metastasis in the rat lung squamous cell carcinoma.Methods： Squamous cell carcinoma of lung was induced with 3-methylcholanthrene in iodized oil by left intra-bronchial instillation in 80 Wistar rats.To obtain specimens in every pathological phase during the carcinogenesis,these rats were sacrificed at different intervals.Expression of Cav-1 and Caspase-3 proteins in each pathological phase during the carcinogenesis was examined by immunohistochemical method.The immunohistochemical scores（IHS） were calculated by combining an estimate of the percentage of immunoreactive cells with that of the stain intensity.Expression of Cav-1 protein was also detected by Western blot.Results： Of all the 155 specimens,the pathological results showed 14 hyperplasia,25 squamous metaplasia,35 dysplasia,12 carcinoma in situ,54 infiltrating carcinoma and 15 metastatic carcinoma.High expression of Cav-1 was shown in normal lung tissues.IHS of Cav-1 was significantly decreased in dysplasia,precancerous lesions and carcinoma in situ（all P0.01）.IHS of Cav-1 significantly increased gradually from carcinoma in situ,infiltrating carcinoma to metastatic carcinoma（P0.05）.There was 80.00% Caspase-3 expression in bronchia mucosal epithelium of control group.IHS of Caspase-3 significantly decreased in hyperplasia,infiltrating carcinoma and metastatic carcinoma（P0.01）.There was no correlation between the expression of Cav-1 and Caspase-3（r=0.035,P=0.771） in the control and experimental groups.Conclusion： The dynamic change of Cav-1 expression is closely correlated with the carcinogenesis of lung cancer.Caspase-3 may also take part in the development and progress of lung cancer.