上皮性卵巢癌组织中COX-2表达及塞来昔布对卵巢癌细胞株生长抑制作用的研究

Expression of cyclooxygenase-2 in epithelial ovarian carcinoma and the effect of a selective cyclooxygenase-2 inhibitor celecoxib on cell line

目的:探讨环氧合酶-2(cyclooxygenase-2,COX-2)在上皮性卵巢癌中的表达及其选择性抑制剂塞来昔布对卵巢癌细胞株生长的影响。方法:应用免疫组化的方法检测正常卵巢、卵巢良性肿瘤、上皮性卵巢癌组织及卵巢癌细胞株OVCAR3、SKOV3中COX-2的表达,采用四甲基偶氮唑蓝(MTT)快速比色法、吖啶橙/溴化乙锭(AO/EB)染色结合荧光显微镜等技术,研究塞来昔布对OVCAR3细胞增殖和凋亡的影响。结果:COX-2在上皮性卵巢癌组织中高表达,阳性率为71.1%,而在正常卵巢和良性卵巢肿瘤中未见表达。COX-2在上皮性卵巢癌组织中的表达与临床分期、组织学类型、组织学分级无关(P>0.05),而与淋巴结转移有关(P<0.05)。塞来昔布可抑制OVCAR3、SKOV3细胞生长,呈浓度和时间依赖性,S-N-K分析及最小显著差(LSD)检验组间两两比较,P均<0.05。荧光显微镜下见典型的凋亡形态学改变,凋亡比例呈剂量和时间依赖,S-N-K分析组间两两比较,P均<0.05。结论:上皮性卵巢癌组织及细胞株OVCAR3、SKOV3中存在COX-2表达,塞来昔布可抑制卵巢癌细胞增殖,并诱导细胞凋亡,塞来昔布可能成为卵巢癌化疗的有效药物。

Objective： To study on the expression of cyclooxygenase-2 in epithelial ovarian carcinoma and the effect of a selective cyclooxygenase-2 inhibitor celecoxib on cell line. Methods： The expressionof COX-2 was examined by immunohistochemical staining in epithelial ovarian carcinoma, benign ovarian neoplasm,normal controls and ovarian carcinoma cell line. By using MTT assay, acridine orange and ethidium bromide staining, the effect of celecoxib on the proliferation and apoptosis of ovarian carcinoma cell line was tested. Results： COX-2 expression was high in ovarian epithelial carcinoma with a positive rate of 71.1%, Whereas COX-2 expression was not found in benign ovarian neoplasm and normal controls. COX-2 expression also was found in ovarian carcinoma cell line. The positive expression of COX-2 had no correlation with clinical stage, pathologic differentiation and histological types（P〉0.05）, but it correlated with lymphnode metastasis（P〈0.05）. The growth of OVCAR3, SKOV3 cells was inhibited by celecoxib in a dose- and time- dependent manners. S-N-K analysis and LSD test all displayed difference （P〈0.05）. The treated OVCAR3 ceils exhibited some mophological features of apoptosis.The apoptotic index of which was in a dose- and time- dependent manners, S-N-K analysis displayed P〈0.05. Conclusion： The expression COX-2 and VEGF-C is found in ovrian epithelial carcinoma and its cell lines .The growth of ovrian carcinoma cell lines can be inhibited by celecoxib. Celecoxib may be used as chemotherapeutic agents for ovarian cancer.