Li Xiping, Liu Xuyi, Wang Jie, Wang Zengli, Jiang Wei, Reed Eddie, Zhang Yi, Liu Yuanlin, Li Q Quentin
Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University Robert C. Byrd Health Sciences Center, Morgantown, WV 26506, USA.
Anticancer Res. 2003 May-Jun;23(3B):2481-7.
Anti-angiogenic therapy represents one of the most promising treatment modalities for human cancer. Thalidomide (alpha-N-phthalimidoglutarimide) is a potent inhibitor of angiogenesis, and it is reported to overcome classical drug resistance in human multiple myeloma cells. However, the effect of this agent on the expression of angiogenic growth factors in cisplatin-resistant tumors is largely unknown. In the current study, we showed that thalidomide suppressed the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cisplatin-resistant human A549DDP lung carcinoma cells. The mRNA levels of VEGF and bFGF were markedly decreased in the A549DDP cells treated with the therapeutic concentrations of thalidomide (0.6-6 micrograms/ml), as determined by RT-PCR analysis. Consistent with these results, thalidomide also significantly reduced the protein levels of VEGF and bFGF in these cells in a dose- and time-dependent manner. This study provided evidence to support the potential therapeutic applications of thalidomide in cisplatin-resistant human lung cancer and other tumors.
抗血管生成疗法是治疗人类癌症最有前景的治疗方式之一。沙利度胺（α-N-邻苯二甲酰谷氨酸）是一种有效的血管生成抑制剂，据报道它能克服人类多发性骨髓瘤细胞中的经典耐药性。然而，该药物对顺铂耐药肿瘤中血管生成生长因子表达的影响在很大程度上尚不清楚。在当前研究中，我们发现沙利度胺可抑制顺铂耐药的人A549DDP肺癌细胞中血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）的表达。通过逆转录聚合酶链反应（RT-PCR）分析确定，用治疗浓度（0.6 - 6微克/毫升）的沙利度胺处理的A549DDP细胞中，VEGF和bFGF的mRNA水平显著降低。与这些结果一致，沙利度胺还以剂量和时间依赖性方式显著降低了这些细胞中VEGF和bFGF的蛋白水平。本研究为支持沙利度胺在顺铂耐药的人肺癌及其他肿瘤中的潜在治疗应用提供了证据。
