Melatonin Differentially Modulates NF-κB Expression in Breast and Liver Cancer Cells
Melatonin Differentially Modulates NF-κB Expression in Breast and Liver Cancer Cells
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DOI：
10.2174/1871520618666180131112304
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发表时间：
2018-01-01
影响因子：
2.8
通讯作者：
Zuccari, Debora A. P. C.
中科院分区：
文献类型：
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作者：
Colombo, Jucimara;Jardim-Perassi, Bruna, V;Zuccari, Debora A. P. C.
背景资料：NF-κ B（nuclear factor kappa B）是由p50和p65两个亚基组成的转录因子，在炎症过程中起关键作用。褪黑激素具有抑瘤、抗血管生成和抗转移的特性，并且最近的一些研究表明褪黑激素在某些类型的癌症中对NF-kB具有抑制作用。本研究旨在探讨褪黑素治疗对乳腺癌和肝癌模型中NF-κ B表达的影响。方法：乳腺癌异种移植模型采用雌性Balb/c裸鼠，皮下注射MDA-MB-231细胞。动物用40 mg/Kg褪黑激素治疗21天。用数字卡尺测量肿瘤体积。采用体外培养的HepG 2细胞建立肝癌模型，用1 mM褪黑素处理24 h。分别采用免疫组化和免疫细胞化学方法检测NF-κ B蛋白的表达，并采用光密度法、体内研究和体外研究对NF-κ B蛋白的表达进行定量。结果：褪黑素治疗组裸鼠乳腺癌移植瘤体积明显缩小（P=0.0022）;褪黑素治疗组小鼠的NF-κ B蛋白染色（P=0.0027）和基因表达（P=0.0185）减少。肝癌模型则相反。结论：褪黑素能降低乳腺癌细胞NF-κ B基因和蛋白的表达，而上调肝癌细胞NF-κ B转录因子的表达。这些数据强调了NF-κ B表达的双重作用，这取决于细胞类型。需要进一步的研究来更好地阐明褪黑激素在NF-κ B中的作用，因为这种转录因子作用于不同的信号通路，这些通路是致癌的基础。
Background: NF-kB (nuclear factor kappa B) is a transcription factor composed of two subunits, p50 and p65, which plays a key role in the inflammatory process. Melatonin has oncostatic, antiangiogenic and antimetastatic properties, and some recent studies have indicated an inhibitory effect of melatonin on NF-kB in some types of cancer. This work aims to investigate the effects of melatonin treatment on the expression of NF-kB in breast and liver cancer models.Method: The breast cancer xenographic model was performed using female Balb/c nude athymic mice injected with MDA-MB-231 cells. The animals were treated with 40 mg/Kg of melatonin for 21 days. Volume of the tumors was measured with a digital caliper. Hepatocarcinonia model was developed by using the HepG2 cells in vitro, treated with 1 mM melatonin for 24 h. The expression of NF-kB protein was verified by immunohistochemistry and immunocytochemistry and quantified by optical densitometry, in vivo study and in vitro study, respectively. NF-kB gene expression was performed by quantitative RT-PCR.Results: The breast cancer xenografts nude mice treated with melatonin showed reduced tumor size (P=0.0022). There was a decrease in NF-kB protein staining (P=0.0027) and gene expression (P=0.0185) in mice treated with melatonin. The opposite results were observed for the hepatocarcinoma model. HepG2 cells treated with melatonin showed an increase in the NF-kB immunostaining when compared to control cells (P=0.0042).Conclusion: Our results indicated that the treatment with melatonin was able to decrease both gene and protein expressions of NF-kB in breast cancer cells and, conversely, increase the transcription factor protein expression in hepatocarcinoma cells. These data highlighted a double role in the expression of NF-kB, depending on the cell type. Further studies are needed to better elucidate the action of melatonin in NF-kB, since this transcription factor acts on different signaling pathways that are fundamental for carcinogenesis.