环氧合酶2和半胱氨酸蛋白水解酶3在大鼠肺鳞癌发生中的作用  

Roles of cyclooxygenase-2 and caspase-3 expression in pathogenesis of lung carcinoma: an experiment with rats

作　　者：陈福春 潘琦 张玉霞[2] 陈洪雷[2] 李红钢[2] 陶鸿潮 杨飞[2] 夏东[2] 刘铭球[2] 

机构地区：[1]浙江省温岭市中医院胸外科,317500 [2]武汉大学医学院病理学系

出　　处：《中华医学杂志》2005年第27期1916-1920,共5页National Medical Journal of China

基　　金：国家自然科学基金资助项目(39870305)

摘　　要：目的检测环氧合酶2(COX2)和半胱氨酸蛋白水解酶3(caspase3)蛋白在甲基胆蒽诱导的大鼠肺鳞癌形成过程中的差异表达并探讨其意义。方法采用左肺叶支气管灌注含甲基胆蒽10mg和二乙基亚硝胺0.01ml的碘油溶液诱发Wistar大鼠的肺鳞癌,应用免疫组织化学SP法检测肺鳞癌发生过程中各阶段组织COX2、caspase3的蛋白表达并计算免疫组织化学评分(IHS)。结果实验组多个阶段病变共存的动物标本有80.0%(64/80),其中获取支气管膜上皮增生14份,鳞状化生25份,不典型增生35份,原位癌12份,侵袭癌54份,转移癌15份。正常支气管黏膜上皮偶有COX2弱阳性表达,不典型增生、原位癌及转移癌阶段COX2的IHS逐步增高,差异有高度显著性(均P<0.01)。10例对照组大鼠支气管粘膜上皮细胞中8例(80.0%)有caspase3的阳性表达,不典型增生、浸润癌和转移癌阶段caspase3的HIS逐步降低,差异有显著性(P<0.01、P<0.01、P<0.05)。在对照组和实验组共165例大鼠肺组织病变中,COX2与caspase3呈显著负相关(χ2=106.664,spearman相关系数为-0.678,P<0.01)。结论COX2蛋白上升和caspase3蛋白减少与肺癌的形成密切相关,二者相互作用,共同促进肺癌的发生和侵袭转移。Objective To investigate the dynamic expression of cyclooxygenase-2 (COX-2) and caspase-3 during the carcinogenesis, invasion and metastasis of 3-methylcholanthrene (MCA) and diethyinitrosamine (DEN)-induced rat lung cancer and its significance. Methods Iodized oil with MCA and DEN was instilled into the left bronchi of 80 Wistar rats to induce squamous cell lung carcinoma. Iodized oil without MCA and DEN was instilled into the left bronchi of 10 rats as control group. Sixteen rats in the experimental group and 2 rats in the control group were killed 10, 15, 35, 60, and 270 days after experiment respectively to undergo pathological examination. Immunohistochemistry was used to detect the protein expression of COX-2 and caspase-3 in the bronchial endothelial cells. Immunohistochemical scores (IHS) were calculated. Results Pathological changes of different phases, such as hyperplasia of bronchial mucosal endothelial cells (14 cases), squamous metaplasia (25 cases), atypical proliferation (35 cases), carcinoma in situ (12 cases), infiltrative carcinoma (54 cases), and metestatic carcinoma (15 cases) appeared successively in the left lung mucosal endothelium of the experimental group. Weak expression of COX-2 protein was occasionally seen in the normal bronchial mucosal endothelium. COX-2 protein expression was becoming stronger and the IHS was becoming higher along with the development of carcinoma (P<0.01). Caspace-2 protein expression was positive in 8 of the 10 (80%) of the control rats with an HIS of 5.92±0.9. And caspace-2 protein expression was becoming weaker along with the development of carcinoma (P<0.01 or P<0.05). Significant negative correlation was found between the COX-2 protein expression and caspase-3 expression (P<0.01). Conclusion COX-2 and caspase-3 play important roles in the carcinogenesis of MCA and DEN-induced rat lung squamous cell carcinoma. COX-2 may take part in blocking cell apoptosis by inhibiting caspase-3 activity, thereby promoting the carcinogenesis of lung cancer. The imbalance bet

关 键 词：蛋白水解酶 半胱氨酸 环氧合酶2 caspase-3蛋白 癌发生 免疫组织化学SP法 Wistar大鼠 不典型增生 COX-2蛋白 鼠肺 二乙基亚硝胺 粘膜上皮细胞 甲基胆蒽 阳性表达 支气管灌注 支气管黏膜 肺组织病变 肺鳞癌 转移癌 差异表达 

分 类 号：R734.2[医药卫生—肿瘤]