摘要
目的探讨环氧合酶-2(COX-2)对人乳腺癌淋巴管形成的影响。方法1998年11月至2002年3月行手术治疗并经病理证实的乳腺癌患者94例,随访83例,失访11例。免疫组织化学方法检测COX-2、血管内皮生长因子-C(VEGF—C)及D2-40在乳腺癌中的表达。逆转录聚合酶链式反应(RT-PCR)和Western印迹法分别检测加入不同浓度COX-2抑制剂尼美舒利后VEGF-CmRNA及蛋白的变化。Western印迹法检测加入外源性前列腺素E2(PGE2)和曲妥珠单抗后VEGF—C蛋白的变化。结果46.8%的乳腺癌组织呈COX-2高表达,51.1%呈VEGF—C高表达。COX-2与VEGF—C(P〈0.01)、淋巴管密度(P=0.032)和淋巴结转移(P=0.035)呈正相关,与乳腺癌患者的无病生存率(P=0.010)和总生存率(P=0.040)呈负相关。尼美舒利以剂量依赖性方式下调VEGF-CmRNA及蛋白表达,而PGE2上调其蛋白表达。曲妥珠单抗可显著降低VEGF—C的蛋白表达。结论COX-2可通过上调VEGF—C的表达,促进乳腺癌的淋巴管形成和淋巴结转移,并影响乳腺癌患者的预后。
Objective To study the effect of cyclooxygenase-2 (COX-2) on lymphangiogenasis in breast cancer. Methods By the means of immunohistochemistry, COX-2, vascular endothelial growth factor-C (VEGF-C) and D2-40 were examinated in the tissue samples of primary tumors from 94 patients underwent surgical resections for breast cancer from November 1998 to March 2002. Eighty-three patients were followed-up. The expressions of VEGF-C mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot in MDA-MB-231 cell lines by the treatment of selective COX-2 inhibitor Nimesulide at different doses. The expressions of VEGF-C protein were evaluated in MDA-MB-231 cells treated by PGE2 ( 1μg/ml) and Trastuzumab ( 1 μg/ml), respectively. Results COX-2 over-expression was observed in 46. 8% of surgical specimens ( 44/94 ), while VEGF-C over- expression occurred in 51.1% of tumor samples (48/94). COX-2 was strongly correlated with VEGF-C expression(P 〈 0. 01 ), microlymphatic vessels ( P = 0. 032 ) and metastatic lymph nodes ( P = 0. 035 ). Patients with COX-2 positive tumors had a significant shorter survival time than those with negative tumors did, including disease-free survival ( P = 0. 010) and overall survival ( P= 0. 040). Nimesulide could down- regulate the expressions of VEGF-C mRNA and protein in a does-dependent manner, while PGE2 could up- regulate the expressions. The expression of VEGF-C protein up-regulated by PGE2 treatment was decreased by Trastuzumab. Conclusions COX-2 over-expression can up-regulate the expression of VEGF-C. VEGF-C might promote lymph node metastasis by a lymphangiogenic pathway, then affect the prognosis of the patients with breast cancer.
出处
《中华外科杂志》
CAS
CSCD
北大核心
2008年第2期132-135,共4页
Chinese Journal of Surgery
关键词
乳腺肿瘤
前列腺素内过氧化物合酶
内皮生长因子
预后
Breast neoplasms
Prostaglandin-endoperoxide synthase
Endothelial growth factors
Prognosis