Melatonin suppresses migration and invasion via inhibition of oxidative stress pathway in glioma cells
Melatonin suppresses migration and invasion via inhibition of oxidative stress pathway in glioma cells
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DOI：
10.1111/j.1600-079x.2012.00985.x
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发表时间：
2012-09
影响因子：
10.3
通讯作者：
Juntao Wang;Hongbo Hao;Linli Yao;Xiaodan Zhang;Shidou Zhao;E. Ling;A. Hao;Gang Li
中科院分区：
文献类型：
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作者：
Juntao Wang;Hongbo Hao;Linli Yao;Xiaodan Zhang;Shidou Zhao;E. Ling;A. Hao;Gang Li
摘要：褪黑素是一种主要由松果体产生和分泌的吲哚胺，具有多种生理功能，具有抗氧化和抗肿瘤等特性。在本研究中，药理浓度(1 MM)的褪黑素可显著抑制T98G和U251胶质瘤细胞作用24小时后的细胞迁移和侵袭，并抑制基质金属蛋白酶2(MMP2)和MMP9的表达。褪黑素抑制细胞迁移和侵袭的作用与其减少细胞内基础自由基的产生有关。药理浓度的褪黑素还可抑制转录因子核因子轻链增强剂核转录因子轻链增强剂(NF-κB)下游的活性氧物种的结构性激活。此外，NF-κB特异性抑制剂吡咯烷二硫代氨基甲酸酯在10μm处表现出抗迁移和侵袭作用，并抑制MMP2和MMP9的表达，其作用类似于褪黑素。综上所述，褪黑素通过抑制氧化应激途径抑制胶质瘤细胞的迁移和侵袭。这提示褪黑素在脑胶质瘤治疗中具有潜在的治疗应用前景。
Abstract: Melatonin, an indolamine produced and secreted predominately by the pineal gland, exhibits a variety of physiological functions, possesses antioxidant and antitumor properties. In this study, we have shown that pharmacologic concentration (1 mm) of melatonin significantly reduced cell migration and invasion of T98G and U251 glioma cells after 24‐hr treatment and inhibited expression of matrix metalloproteinase 2 (MMP 2) and MMP 9. The melatonin inhibition of cell migration and invasion was associated with its reduction of intracellular basal free radical generation. Melatonin at pharmacologic concentration also inhibited the constitutive activation of the reactive oxygen species downstream transcription factor nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB). Furthermore, pyrrolidine dithiocarbamate, a NF‐κB‐specific inhibitor, at 10 μm displayed anti‐migration and invasion effects and inhibition of MMP 2 and MMP 9 expression resembling that of melatonin. Taken together, it is concluded that inhibition of migration and invasion of glioma cells by melatonin is associated with the latter in its inhibition of oxidative stress pathway. This suggests a potential therapeutic application of melatonin in the treatment of glioma.