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Elucidation of the effect of plumbagin on the metastatic potential of B16F10 murine melanoma cells via MAPK signalling pathway.

白花丹苷通过 MAPK 信号通路对 B16F10 鼠黑色素瘤细胞转移潜能影响的阐明。

  • 影响因子:2.45
  • DOI:10.1111/exd.14079
  • 作者列表:"Alem FZ","Bejaoui M","Villareal MO","Rhourri-Frih B","Isoda H
  • 发表时间:2020-02-03
Abstract

:Melanoma is the most dangerous form of skin cancer with a very poor prognosis. Melanoma develops when unrepaired DNA damage causes to skin cells to multiply and form malignant tumors. The current therapy is limited by the highly ability of this disease to metastasize rapidly. Plumbagin is a naphthoquinone (5-hydroxy-2-methyl-1, 4-naphthoquinone), isolated from the roots of medicinal plant Plumbago zeylanica, and it is widely present in Lawsonia inermis L. It has been shown that plumbagin has an anti-proliferative and anti-invasive activities in various cancer cell lines; however, the anti-cancer and anti-metastatic effects of plumbagin are largely unknown against melanoma cells. In this study, we evaluated the effect of plumbagin on B16F10 murine melanoma cells . Plumbagin decreased B16F10 cell viability as well as the cell migration, adhesion, and invasion. The molecular mechanism was studied, and plumbagin downregulated genes relevant in MAPK pathway, matrix metalloproteinases (MMP's), and cell adhesion. Furthermore, plumbagin elevated the expression of apoptosis and tumors suppressor genes, and genes significant in reactive oxygen species (ROS) response. Taken together, our findings suggest that plumbagin has an anti-invasion and anti-metastasis effect on melanoma cancer cells by acting on MAPK pathway and its related genes.

摘要

: 黑色素瘤是最危险的皮肤癌,预后极差。当未修复的 DNA 损伤导致皮肤细胞增殖并形成恶性肿瘤时,黑色素瘤就会发展。目前的治疗受到这种疾病快速转移的高度能力的限制。白花丹素是一种萘醌 (5-羟基-2-甲基-1,4-萘醌),从药用植物白花丹的根部分离得到,广泛存在于 Lawsonia inermis L 中。研究表明,白花丹素在各种癌细胞系中具有抗增殖和侵袭活性; 然而, 白花丹素对黑色素瘤细胞的抗癌和抗转移作用在很大程度上是未知的。在本研究中,我们评价了白花丹素对 B16F10 鼠黑色素瘤细胞的影响。白花丹素降低 B16F10 细胞活力以及细胞迁移、粘附和侵袭。对其分子机制进行了研究,并对 MAPK 通路、基质金属蛋白酶 (MMP) 和细胞粘附相关基因进行了研究。此外,白花丹素能提高细胞凋亡和肿瘤抑制基因的表达,以及活性氧 (ROS) 反应中显著的基因。总之,我们的研究结果表明,白花丹苷通过作用于 MAPK 通路及其相关基因,对黑色素瘤癌细胞具有抗侵袭和抗转移作用。

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