Melatonin modulates the expression of VEGF and HIF-1α induced by CoCl2 in cultured cancer cells
Melatonin modulates the expression of VEGF and HIF-1α induced by CoCl2 in cultured cancer cells
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DOI：
10.1111/j.1600-079x.2007.00498.x
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发表时间：
2008-03-01
影响因子：
10.3
通讯作者：
Xiu, Ruijuan
中科院分区：
文献类型：
--
作者：
Dai, Min;Cui, Peilin;Xiu, Ruijuan
褪黑激素是一种重要的天然抑瘤剂。目前还没有关于其对肿瘤血管生成的可能影响的数据，这是负责肿瘤生长和扩散的主要生物学机制。血管内皮生长因子（VEGF）在实体瘤的血管生成和发展中起着重要作用。为了研究褪黑激素对血管生成的可能影响，我们研究了褪黑激素对三种人癌细胞系（PANC-1，HeLa和A549细胞）内源性VEGF表达的影响。在这项研究中，我们报告说，生理浓度的褪黑激素对VEGF的表达没有明显的影响，而药理浓度的褪黑激素抑制VEGF的mRNA和蛋白水平诱导的低氧模拟氯化钴（CoCl 2）。褪黑激素还降低缺氧诱导因子（HIF）-1 α蛋白水平，表明转录因子HIF-1在抑制VEGF表达中的作用。药理浓度的褪黑激素在常氧条件下对VEGF和HIF-1 α的影响尚不确定，这表明在CoCl 2存在或不存在的情况下VEGF的调节机制是不同的，可能涉及其他或额外的转录因子。总之，我们的数据表明，高浓度的褪黑激素显着降低内源性VEGF和HIF-1 α的表达诱导的CoCl 2在培养的癌细胞。
Melatonin is an important natural oncostatic agent. At present there are no data available as to its possible influence on tumor angiogenesis, which is a major biological mechanism responsible for tumor growth and dissemination. It is well known that vascular endothelial growth factor (VEGF) is crucial to a solid tumor's higher vascularization and development. To investigate the possible influence of melatonin on angiogenesis, we studied the effect of melatonin on endogenous VEGF expression in three human cancer cell lines (PANC-1, HeLa and A549 cells). In this study, we report that physiologic concentrations of melatonin have no obvious impact on the VEGF expression, whereas pharmacologic concentrations of melatonin suppress the VEGF mRNA and protein levels induced by hypoxia mimetic cobalt chloride (CoCl2). Melatonin also decreases hypoxia-inducible factor (HIF)-1 alpha protein levels, suggesting a role for transcription factor HIF-1 in the suppression of VEGF expression. The effect of pharmacologic concentrations of melatonin on VEGF and HIF-1 alpha under normoxia is uncertain, which indicates that the regulatory mechanisms of VEGF in the absence or presence of CoCl2 are different and other or additional transcription factors may be involved. Taken together, our data show that melatonin in high concentrations markedly reduces the expression of endogenous VEGF and HIF-1 alpha induced by CoCl2 in cultured cancer cells.