环氧化酶-2及其抑制剂与结直肠癌微血管和淋巴管生成的研究

Relation of COX-2 expression and its inhibitor with angiogenesis and lymphangiogenesis in colorectal adenocarcinoma

目的探讨环氧化酶-2(COX-2)在结直肠癌组织的表达与肿瘤生物学特征、微血管生成及淋巴管生成的关系及其抑制剂塞来昔布的抗肿瘤作用和机制。方法应用免疫组化方法检测64例结直肠癌组织中COX-2的表达、微血管形成及淋巴管生成,分析其相关性及与临床病理参数联系。临床晚期直肠癌患者7例,给予塞来昔布灌肠治疗15天,对活检肿瘤组织微血管及淋巴管进行对比。结果COX-2的表达与结直肠癌的分期(P=0.003)和组织学类型(P=0.004)相关;COX-2高表达组微血管密度(M VD)和淋巴管密度(LVD)均高于COX-2低表达组(P<0.05)。塞来昔布灌肠治疗后直肠癌微血管密度下降,淋巴管密度无差异。结论COX-2可能通过促进淋巴管及微血管生成参与了结直肠癌的发生与发展。COX-2抑制剂塞来昔布可抑制直肠癌微血管生成。

Objective To investigate the relationships among the expression of cyclooxygenase-2 （COX-2） ,microvessel density（MVD） and lymphatic vessel density（LVD） in colorectal adenocarcinoma and to explore the antitumor effects of COX- 2 specific inhibitor celecoxib. Methods The expressions of COX-2,MVD and LVD were studied by immunohistochemistry in 64 cases of colorectal adenocarcinomas, and the relationships among COX-2 , MVD , LVD and the clinicopathological characteristics were analyzed. Seven cases of advanced colorectal cancer whose tumor could not be removed,were treated with celecoxib enema twice a day for fifteen days,the changes of LVD and MVD were evaluated. Results The expression of COX- 2 was correlated with tumor stage （P = 0. 003） and histological type （P= 0. 004） in colorectal carcinoma. MVD and LVD in COX-2 strong expression group were higher than those in COX-2 weak expression group （P〈0.05）. Treatment of celecoxib enema could reduce MVD but not LVD in colorectal carcinoma. Conclusion COX-2 may be involved in the tumor formation and development of colorectal adenocarcinoma through promotion of angiogenesis and lymphangiogenesis. Celecoxib enema might suppress angiogenesis in colorectal adenocarcinoma.