Li Xiping, Liu Xuyi, Wang Jie, Wang Zengli, Jiang Wei, Reed Eddie, Zhang Yi, Liu Yuanlin, Li Q Quentin
Mary Babb Randolph Cancer Center, West Virginia University, Robert C. Byrd Health Sciences Center, Morgantown, WV 26506, USA.
Int J Mol Med. 2003 Jun;11(6):785-90.
Angiogenesis is a critical step for the growth and metastasis of solid tumors, and it is a major therapeutic target for the development of anti-angiogenics for cancer treatment. Thalidomide is reported to be an anti-angiogenic agent, which is currently in phase II clinical trials for the treatment of advanced malignancies. However, the mechanism of thalidomide in angiogenesis is not completely understood. This study was undertaken to investigate the effect of thalidomide on the expression of angiogenesis growth factors in human lung cancer cells. In this report, we show that thalidomide downregulated the mRNA and protein expression of basic fibroblast growth factor (bFGF) in the human lung adenocarcinoma cell line A549, and that the effect of thalidomide was time and concentration-dependent. In contrast, the expression of vascular endothelial growth factor (VEGF) by thalidomide in these cells was in two phases. The mRNA and protein expression of VEGF was increased in the lung cancer cells treated with 0.6-6 microg/ml thalidomide, while higher concentrations of thalidomide decreased VEGF levels significantly in these cells. These data suggest that the anti-angiogenic or antitumor activity of thalidomide may be partly mediated through the regulation of the levels of angiogenesis growth factors.
血管生成是实体瘤生长和转移的关键步骤，也是开发用于癌症治疗的抗血管生成药物的主要治疗靶点。据报道，沙利度胺是一种抗血管生成剂，目前正处于治疗晚期恶性肿瘤的II期临床试验阶段。然而，沙利度胺在血管生成中的作用机制尚未完全明确。本研究旨在探讨沙利度胺对人肺癌细胞血管生成生长因子表达的影响。在本报告中，我们发现沙利度胺可下调人肺腺癌细胞系A549中碱性成纤维细胞生长因子（bFGF）的mRNA和蛋白表达，且沙利度胺的作用具有时间和浓度依赖性。相比之下，沙利度胺对这些细胞中血管内皮生长因子（VEGF）的表达有两个阶段的影响。在0.6 - 6微克/毫升沙利度胺处理的肺癌细胞中，VEGF的mRNA和蛋白表达增加，而更高浓度的沙利度胺则显著降低了这些细胞中的VEGF水平。这些数据表明，沙利度胺的抗血管生成或抗肿瘤活性可能部分是通过调节血管生成生长因子的水平来介导的。
