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环氧化酶-2及其选择性抑制剂尼美舒利对乳腺癌作用机制的研究

Studies on the Effects and mechnisms of COX-2 and Nimesulide on Breast Cancer

【作者】 郭贵龙

【导师】 姚榛祥;

【作者基本信息】 重庆医科大学 , 外科学, 2003, 博士

【摘要】 第一部分 环氧化酶-2在人乳腺癌中的表达及其对肿瘤新生血管形成的影响第一节 环氧化酶-2在人乳腺癌中的表达和临床意义目的:本研究旨在探讨COX-2在乳腺癌组织中的表达和临床意义。方法:应用逆转录聚合酶链反应(RT-PCR)、免疫组化法及蛋白印迹法(Western blot)分别检测人乳腺癌组织及配对的癌旁组织、远离肿瘤正常乳腺组织的COX-2mRNA及其蛋白表达。结果:86%的癌组织COX-2mRNA表达显著增高(0~1.180);正常乳腺组织几乎不表达;癌旁组织表达明显增高(0~0.652)。癌与癌旁组织、正常乳腺组织COX-2mRNA的表达差异有显著性意义(P<0.05)。免疫组化显示乳腺癌组织46.5%COX-2呈高表达;癌旁组织16%为高表达,两者比较差异有显著性意义(P<0.05);正常乳腺组织未见COX-2蛋白表达。Western blot表明乳腺癌组织蛋白水平明显增高(52.27±11.64),癌旁组织COX-2蛋白也升高(14.42±3.82),正常乳腺无COX-2的表达。结论:COX-2基因及其蛋白的表达增高发生在乳腺上皮细胞癌变的早期,在大多数肿瘤组织COX-2的表达明显升高,而正常乳腺组织并不表达,提示COX-2可作为乳腺癌早期预防之靶的。关键词:乳腺癌,环氧化酶-2,蛋白印迹,RT-PCR,免疫组化

【Abstract】 Part OneTHE EXPRESSION AND CLINICAL SIGNIFICANCE OF COX-2 IN BREAST CANCER, AND THE EFFECTOF COX-2 ON ANGIOGENESIS SECTION ONE THE EXPRESSION AND CLINICAL SIGNIFICANCEOF CYCLOOXYGENASE-2 IN BREAST CANCERObjectives: To investigate the expression and clinical significance of COX-2 expression. Methods: Reverse transcription-PCR, immunohisto-chemistry, Western blot assay were used to assess the expressions of COX-2 in cancerous tissues, paired tissues adjacent to breast cancers and normal tissues far from neoplasm. Results: Strong expression of COX-2 mRNA was detected in 86% of breast cancers ( 0~1.180 ), and increased expression in paired tissues adjacent to cancers with range of 0~0.652, but nearly no expression in normal tissues. There were significantly different expressions of COX-2 mRNA between cancers and paired tissues adjacent to cancers or normal tissues. Immunohistochemical analysis shown that COX-2 were overexpressed in 46.5% carcinomas, and 16% of paired tissues adjacent to cancers, no expression in normal tissues. Western blot indicated that markedly increased expressions of COX-2 in tumors, while lesser increase in paired tissues and no<WP=13>expression in normal tissues. Conclusions: Overexpression of COX-2 has occurred in the earlier period during tumorigenesis. Selective COX-2 inhibitors may be useful in the chemoprevention and therapy of human breast cancer.KEY WORDS: breast cancer, cox-2, gene, reverse transcription polymerase chain reaction, immunohistochemistry

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