Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Recent Pat Anticancer Drug Discov. 2020;15(4):329-340. doi: 10.2174/1574892815666200929145236.
The Notch signaling pathway has a key role in angiogenesis and Delta - Like Ligand 4 (DLL4) is one of the main ligands of Notch involved in cell proliferation in sprouting vessels.
In this study, we aimed to evaluate the expression of DLL4 in primary breast tumors and to examine the effect of melatonin on DLL4 expression in vitro.
Eighty-five breast tumor and paired adjacent non-tumor tissue samples were collected. Apoptosis assay was performed on breast cancer cells to evaluate melatonin effects. Western blot and quantitative RT-PCR were used to measure DLL4 expression. Then, we investigated the effect of melatonin on the expression of DLL4 in four breast cancer cell lines at RNA and protein levels. We also performed a probabilistic neural network analysis to study genes closely associated with DLL4 expression.
Our results showed a significantly higher expression of DLL4 in tumor tissues compared to non-tumor tissues (P = 0.027). Melatonin treatment substantially attenuated DLL4 expression in BT474 and MCF-7 cells, but not in SK-BR-3 and MDA-MB-231 cells. Also, melatonin induced apoptosis in all four cell lines. Network analysis revealed a set of 15 genes that had close association and interaction with DLL4. DLL4 was overexpressed in breast cancer tissues as compared to the non-tumor tissues.
It can be concluded that melatonin treatment attenuated DLL4 expression only in estrogen- responsive breast cancer cells and is able to induce apoptosis in breast cancer cells.
Notch 信号通路在血管生成中具有关键作用，Delta 样配体 4（DLL4）是 Notch 的主要配体之一，参与芽生血管中的细胞增殖。
本研究旨在评估 DLL4 在原发性乳腺癌肿瘤中的表达，并研究褪黑素对体外 DLL4 表达的影响。
收集 85 例乳腺癌肿瘤和配对的相邻非肿瘤组织样本。对乳腺癌细胞进行凋亡实验，以评估褪黑素的作用。采用 Western blot 和定量 RT-PCR 检测 DLL4 的表达。然后，我们在四个乳腺癌细胞系中研究了褪黑素对 DLL4 表达的影响，包括 RNA 和蛋白水平。我们还进行了概率神经网络分析，以研究与 DLL4 表达密切相关的基因。
我们的结果表明，肿瘤组织中 DLL4 的表达明显高于非肿瘤组织（P = 0.027）。褪黑素处理显著减弱了 BT474 和 MCF-7 细胞中 DLL4 的表达，但对 SK-BR-3 和 MDA-MB-231 细胞没有影响。此外，褪黑素诱导了所有四个细胞系的凋亡。网络分析显示了一组与 DLL4 密切关联和相互作用的 15 个基因。与非肿瘤组织相比，DLL4 在乳腺癌组织中过度表达。
褪黑素治疗仅在雌激素反应性乳腺癌细胞中减弱 DLL4 表达，并能诱导乳腺癌细胞凋亡。
