Melatonin inhibits the proliferation of human osteosarcoma cell line MG-63
Melatonin inhibits the proliferation of human osteosarcoma cell line MG-63
复制标题
褪黑素抑制人骨肉瘤细胞系MG-63的增殖
DOI：
10.1016/j.bone.2013.02.021
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发表时间：
2013-08-01
期刊：
影响因子：
4.1
通讯作者：
Reiter, Russel J.
中科院分区：
文献类型：
--
作者：
Liu, Lifeng;Xu, Ying;Reiter, Russel J.
骨肉瘤的发生和褪黑激素的减少似乎是平行的;这表明癌症抑制剂褪黑激素的减少可能有助于骨肉瘤的发生，补充褪黑激素可能有希望防止这种情况的发展和进展。然而，没有直接证据表明褪黑激素在骨肉瘤细胞中具有抗增殖作用。在目前的研究中，我们研究了褪黑激素是否抑制人骨肉瘤细胞系MG-63的增殖。MTT染色显示，在4 mM-10 mM浓度范围内，褪黑素以剂量依赖和时间依赖的方式显著抑制MG-63细胞的增殖。流式细胞术证明，4 mM褪黑激素显著增加了细胞周期G（0）/G（1）期的细胞比例，同时降低了S和G（2）/M期的比例。Western blot和实时定量PCR分析进一步证实褪黑素的抑制作用可能是通过下调与G（1）期相关的cyclin D1和CDK 4以及与G（2）/M期相关的cyclin B1和CDK 1来实现的。与G（1）/S转换和S期相关的cyclin E、CDK 2和cyclin A表达无下调。这些结果提供了证据表明，褪黑激素可以显着抑制人骨肉瘤细胞增殖的剂量依赖性和时间依赖性的方式，这种抑制涉及下调细胞周期蛋白D1，CDK 4，细胞周期蛋白B1和CDK 1。皇冠版权所有（C）2013由Elsevier Inc.发布。All rights reserved.
It seems established that the onset of osteosarcoma and the reduction in melatonin production run in parallel; this suggests that the decline in the cancer-inhibiting agent, melatonin, may contribute to the occurrence of osteosarcoma and that melatonin supplementation may have promise for preventing the development and progression of this condition. There is, however, no direct evidence regarding an antiproliferative effect of melatonin in osteosarcoma cells. In the current study, we examined whether melatonin inhibits the proliferation of human osteosarcoma cell line MG-63. MTT staining showed that at 4 mM-10 mM concentrations, melatonin significantly reduced the MG-63 cell proliferation in a dose-dependent and time-dependent manner. Flow cytometry documented that 4 mM melatonin significantly increased the fraction of cells in the G(0)/G(1) phase of the cell cycle, while simultaneously reducing the proportion in the S and G(2)/M phases. Western blot and real-time PCR analyses further confirmed that melatonin's inhibitory effect was possibly because of downregulation of cyclin D1 and CDK4, related to the G(1) phase, and of cyclin B1 and CDK1, related to the G(2)/M phase. There was no downregulation of cyclin E, CDK2, and cyclin A, which are related to G(1)/S transition and S phase. These findings provide evidence that melatonin may significantly inhibit human osteosarcoma cell proliferation in a dose-dependent and time-dependent manner and this inhibition involves the downregulation of cyclin D1, CDK4, cyclin B1 and CDK1. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.