Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou (510080), Guangdong, People's Republic of China.
J Exp Clin Cancer Res. 2011 Jan 10;30(1):6. doi: 10.1186/1756-9966-30-6.
Vascular endothelial growth factor (VEGF) expression is up-regulated via a cyclooxygenase-2 (COX-2)-dependent mechanism in non-small cell lung cancer (NSCLC), but the specific signaling pathway involved is unclear. Our aim was to investigate the signaling pathway that links COX-2 with VEGF up-regulation in NSCLC.
COX-2 expression in NSCLC samples was detected immunohistochemically, and its association with VEGF, microvessel density (MVD), and other clinicopathological characteristics was determined. The effect of COX-2 treatment on the proliferation of NSCLC cells (A549, H460 and A431 cell lines) was assessed using the tetrazolium-based MTT method, and VEGF expression in tumor cells was evaluated by flow cytometry. COX-2-induced VEGF expression in tumor cells was monitored after treatment with inhibitors of protein kinase C (PKC), PKA, prostaglandin E2 (PGE2), and an activator of PKC.
COX-2 over-expression correlated with MVD (P = 0.036) and VEGF expression (P = 0.001) in NSCLC samples, and multivariate analysis demonstrated an association of VEGF with COX-2 expression (P = 0.001). Exogenously applied COX-2 stimulated the growth of NSCLCs, exhibiting EC50 values of 8.95 × 10(-3), 11.20 × 10(-3), and 11.20 × 10(-3) μM in A549, H460, and A431 cells, respectively; COX-2 treatment also enhanced tumor-associated VEGF expression with similar potency. Inhibitors of PKC and PGE2 attenuated COX-2-induced VEGF expression in NLCSCs, whereas a PKC activator exerted a potentiating effect.
COX-2 may contribute to VEGF expression in NSCLC. PKC and downstream signaling through prostaglandin may be involved in these COX-2 actions.
血管内皮生长因子 (VEGF) 的表达在非小细胞肺癌 (NSCLC) 中通过环氧化酶-2 (COX-2) 依赖性机制上调，但涉及的具体信号通路尚不清楚。我们的目的是研究将 COX-2 与 NSCLC 中 VEGF 上调相关的信号通路。
免疫组织化学检测 NSCLC 样本中的 COX-2 表达，并确定其与 VEGF、微血管密度 (MVD) 和其他临床病理特征的关系。使用基于四唑的 MTT 法评估 COX-2 处理对 NSCLC 细胞（A549、H460 和 A431 细胞系）增殖的影响，并通过流式细胞术评估肿瘤细胞中 VEGF 的表达。用蛋白激酶 C (PKC)、PKA、前列腺素 E2 (PGE2) 的抑制剂和 PKC 激活剂处理后，监测 COX-2 诱导的肿瘤细胞中 VEGF 的表达。
COX-2 过表达与 NSCLC 样本中的 MVD（P = 0.036）和 VEGF 表达（P = 0.001）相关，多变量分析表明 VEGF 与 COX-2 表达相关（P = 0.001）。外源性应用 COX-2 刺激 NSCLC 生长，在 A549、H460 和 A431 细胞中分别表现出 EC50 值为 8.95×10(-3)、11.20×10(-3) 和 11.20×10(-3) μM；COX-2 处理也以相似的效力增强肿瘤相关的 VEGF 表达。PKC 和 PGE2 的抑制剂减弱了 NLCSCs 中 COX-2 诱导的 VEGF 表达，而 PKC 激活剂则发挥了增强作用。
COX-2 可能有助于 NSCLC 中的 VEGF 表达。PKC 和通过前列腺素的下游信号可能参与这些 COX-2 作用。
