Guo Gui-Long, Yang Guang-Lun, Li Zhuo-Ying, You Jie, Yang Kai, Huang Du-Ping, Hu Xiao-Qu, Zhang Xiao-Hua
Department of Oncological Surgery, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China.
Zhonghua Wai Ke Za Zhi. 2008 Jan 15;46(2):132-5.
To study the effect of cyclooxygenase-2 (COX-2) on lymphangiogenesis in breast cancer.
By the means of immunohistochemistry, COX-2, vascular endothelial growth factor-C (VEGF-C) and D2-40 were examined 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 (1 microg/ml) and Trastuzumab (1 microg/ml), respectively.
COX-2 over-expression was observed in 46.8% of surgical specimens (44/94), while VEGF-C overexpression occurred in 51.1% of tumor samples (48/94). COX-2 was strongly correlated with VEGF-C expression (P < 0.01), micro-lymphatic 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.
COX-2 over-expression can up-regulate the expression of VEGF-C. VEGF-C might promote lymph node metastasis by a lymph-angiogenic pathway, then affect the prognosis of the patients with breast cancer.
研究环氧化酶-2（COX-2）对乳腺癌淋巴管生成的影响。
采用免疫组织化学方法，检测1998年11月至2002年3月间94例行乳腺癌手术切除患者的原发性肿瘤组织样本中的COX-2、血管内皮生长因子-C（VEGF-C）和D2-40。对83例患者进行随访。用不同剂量的选择性COX-2抑制剂尼美舒利处理MDA-MB-231细胞系，通过逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法检测VEGF-C mRNA和蛋白的表达。分别用前列腺素E2（PGE2，1微克/毫升）和曲妥珠单抗（1微克/毫升）处理MDA-MB-231细胞，评估VEGF-C蛋白的表达。
46.8%（44/94）的手术标本中观察到COX-2过表达，而51.1%（48/94）的肿瘤样本中出现VEGF-C过表达。COX-2与VEGF-C表达（P<0.01）、微淋巴管（P = 0.032）和转移淋巴结（P = 0.035）密切相关。COX-2阳性肿瘤患者的无病生存期（P = 0.010）和总生存期（P = 0.040）均显著短于COX-2阴性肿瘤患者。尼美舒利可剂量依赖性下调VEGF-C mRNA和蛋白的表达，而PGE2可上调其表达。曲妥珠单抗可降低PGE2处理上调的VEGF-C蛋白表达。
COX-2过表达可上调VEGF-C的表达。VEGF-C可能通过淋巴管生成途径促进淋巴结转移，进而影响乳腺癌患者的预后。
