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背景与目的:我们以前的研究发现,环氧合酶-2(COX-2)在非小细胞肺癌(NSCLC)上调表达是患者独立预后的不良因素。COX-2参加结肠癌等实体瘤的血管生成,是否参与NSCLC血管生成目前尚有争议。本研究的目的是探讨COX-2表达与血管生成和血管内皮细胞生长因子(VEGF)-A表达之间的关系。方法:用脂质体将表达COX-2反义核酸的质粒和空质粒分别稳定转染H1299细胞(H1299-AS和H1299-P),采用RT-PCT和W esternB lot法检测细胞株COX-2和VEGF-A的水平。应用免疫组织化学染色法检测60例NSCLC肿瘤组织COX-2、VEGF-A和CD31表达情况,用χ2检验分析这些参数间相互关系。结果:H1299-AS细胞株COX-2 mRNA和蛋白水平较H1299-P细胞明显下降;VEGF-A蛋白表达水平亦同步下降。肺腺癌COX-2表达率为77%,显著高于肺鳞癌的37%(P<0.05)。NSCLC中COX-2和VEGF-A表达与肿瘤微血管密度明显相关(r分别为0.55和0.42,P<0.05)。COX-2表达阴性患者肿瘤微血管密度为45.7±15.6根/200×视野,显著高于不表达患者的37.4±9.7根/200×视野(P<0.05)。NSCLC组织中COX-2表达水平和微血管密度与患者术后生存期明显相关(P<0.05)。结论:NSCLC存在COX-2和VEGF-A共表达,COX-2可能通过诱导VEGF-A表达来发挥促血管生成样作用。
BACKGROUND & AIM: Our previous study found that COX-2 upregulation in non-small cell lung cancer (NSCLC) is an adverse prognostic factor in patients. COX-2 is involved in the angiogenesis of solid tumors such as colon cancer. It is still controversial whether it is involved in the angiogenesis of NSCLC. The purpose of this study was to investigate the relationship between COX-2 expression and angiogenesis and the expression of vascular endothelial growth factor (VEGF) -A. METHODS: H1299 cells (H1299-AS and H1299-P) were stably transfected with plasmids and empty plasmids expressing COX-2 antisense oligonucleotides respectively by lipofectamine. The cell lines COX-2 And VEGF-A levels. Immunohistochemical staining was used to detect the expression of COX-2, VEGF-A and CD31 in 60 NSCLC tumor tissues. The relationship between these parameters was analyzed by Chi-square test. Results: The COX-2 mRNA and protein levels in H1299-AS cell line were significantly lower than those in H1299-P cell line. The expression of VEGF-A protein also decreased synchronously. The expression of COX-2 in lung adenocarcinoma was 77%, which was significantly higher than that in squamous cell carcinoma of lung (P <0.05). The expressions of COX-2 and VEGF-A in NSCLC were significantly correlated with the microvessel density (r = 0.55 and 0.42, P <0.05, respectively). The microvessel density in the COX-2 negative patients was 45.7 ± 15.6 roots / 200 × field, which was significantly higher than that in the non-expressed patients (37.4 ± 9.7 roots / 200 × field) (P <0.05). The expression level of COX-2 and microvessel density in NSCLC tissues were significantly correlated with postoperative survival (P <0.05). CONCLUSIONS: COX-2 and VEGF-A are co-expressed in NSCLC. COX-2 may exert pro-angiogenic effect by inducing VEGF-A expression.