大鼠肺鳞癌发生发展中环氧化酶-2和caspase-3的表达和意义

Expression of Cox-2 and caspase-3 during experimental rat lung squamous carcinogenesis

目的 :研究参与炎症的环氧化酶 -2(Cox 2 )和凋亡相关蛋白caspase 3在大鼠肺鳞癌发生发展各阶段的蛋白表达状况并探讨炎症、凋亡和肺癌发生发展的关系。方法 :Wistar大鼠 80只 ,左肺叶支气管灌注含三甲基胆蒽(MCA)和二乙基亚硝胺 (DEN )的碘油溶液 ,分批处死获取肺鳞癌形成过程各阶段标本。免疫组化检测各阶段病变组织Cox 2、caspase 3 的表达并计算免疫组化评分 (IHS)。结果 :79 0 0 %( 4 9/ 62 )的动物标本有多个阶段病变共存 ,共获取支气管膜上皮增生 14例 ,鳞状化生 2 5例 ,不典型增生 3 3例 ,原位癌 12例 ,侵袭癌 5 4例 ,转移癌 17例。正常支气管黏膜上皮偶有Cox 2弱阳性表达 ,随着癌变进展而逐步上调。不典型增生、原位癌及转移癌阶段Cox 2的IHS增高有统计学意义 ,P <0 0 1、P <0 0 5、P <0 0 1。 10例对照组大鼠支气管黏膜上皮细胞中 8例 ( 8/ 10 )有caspase 3的阳性表达 ,随着支气管黏膜上皮的癌变进程表达下降。不典型增生、转移癌阶段caspase 3的HIS降低有统计学意义 ,P <0 0 5、P <0 0 1。在 165例大鼠肺组织病变中 ,Cox 2与caspase 3呈显著负相关 ,χ2 =2 1 675 ,spearman相关系数为 -0 2 46,P =0 0 0 1。结论 :Cox 2、caspase 3均与肺鳞癌的发生和发展过程相关 ,可能是联系炎症。

OBJECTIVE:To investigate expression of cyclooxygenase-2 (Cox-2) and caspase-3 during the rat lung squamous carcinogenesis. METHODS: Eighty Wistar rats were instilled with 3-methylcholanthrene (MCA) and diethylinitrosamine (DEN) into the left lobar branchus to induce lung squamous cell carcinoma. To obtain specimen in every pathological phase during the carcinogenesis, these rats were at different intervals. The protein expression of Cox-2 and caspase-3 in each pathological phases during the carcinogenesis were 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. RESULTS: 155 specimens of every pathological phase during the carcinogenesis showed: hyperplasia 14, squamous metaplasia 25, dysplasia 33, carcinoma in situ 12, infiltrating carcinoma 54 and metastasis 17. Inflammation and elevated expressions of Cox-2 was shown in the precancerous lesions. The Cox-2 IHS was significantly increased in dysplasia, carcinoma in situ and metastasis, P<0.01, P<0.05, P<0.01 respectively. The caspase-3 IHS significantly decreased in hyperplasia and metastasis, P<0.05, P<0.01 respectively. There was a negative correlation between the expression of Cox-2 and caspase-3, χ 2= 21.675, γ=-0.246, P=0.001. CONCLUSIONS: Cox-2 and caspase-3 play important roles in the carcinogenesis of inducing rat lung squamous cell carcinoma by MCA and DEN. Cox-2 may take part in blocking cell apoptosis by inhibiting caspase-3 activity, thereby promote carcinogenesis of lung cancer.