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岩藻依聚糖对葡萄膜黑色素瘤细胞系无抗肿瘤作用。

Fucoidan Does Not Exert Anti-Tumorigenic Effects on Uveal Melanoma Cell Lines.

作者信息

Dithmer Michaela, Kirsch Anna-Maria, Richert Elisabeth, Fuchs Sabine, Wang Fanlu, Schmidt Harald, Coupland Sarah E, Roider Johann, Klettner Alexa

机构信息

Department of Ophthalmology, University of Kiel, University Medical Center, Arnold-Heller-Str. 3, 24105 Kiel, Germany.

Experimental Trauma Surgery, University of Kiel, University Medical Center, Arnold-Heller-Str. 3, 24105 Kiel, Germany.

出版信息

Mar Drugs. 2017 Jun 22;15(7):193. doi: 10.3390/md15070193.

Abstract

BACKGROUND

The polysaccharide fucoidan is widely investigated as an anti-cancer agent. Here, we tested the effect of fucoidan on uveal melanoma cell lines.

METHODS

The effect of 100 µM fucoidan was investigated on five cell lines (92.1, Mel270 OMM1, OMM2.3, OMM2.5) and of 1 µg/mL-1 mg/mL fucoidan in two cell lines (OMM1, OMM2.3). Cell proliferation and viability were investigated with a WST-1 assay, migration in a wound healing (scratch) assay. Vascular Endothelial Growth Factor (VEGF) was measured in ELISA. Angiogenesis was evaluated in co-cultures with endothelial cells. Cell toxicity was induced by hydrogen-peroxide. Protein expression (Akt, ERK1/2, Bcl-2, Bax) was investigated in Western blot.

RESULTS

Fucoidan increased proliferation in two and reduced it in one cell line. Migration was reduced in three cell lines. The effect of fucoidan on VEGF was cell type and concentration dependent. In endothelial co-culture with 92.1, fucoidan significantly increased tubular structures. Moreover, fucoidan significantly protected all tested uveal melanoma cell lines from hydrogen-peroxide induced cell death. Under oxidative stress, fucoidan did not alter the expression of Bcl-2, Bax or ERK1/2, while inducing Akt expression in 92.1 cells but not in any other cell line.

CONCLUSION

Fucoidan did not show anti-tumorigenic effects but displayed protective and pro-angiogenic properties, rendering fucoidan unsuitable as a potential new drug for the treatment of uveal melanoma.

摘要

背景

岩藻多糖作为一种抗癌剂受到广泛研究。在此,我们测试了岩藻多糖对葡萄膜黑色素瘤细胞系的影响。

方法

研究了100 μM岩藻多糖对五种细胞系(92.1、Mel270、OMM1、OMM2.3、OMM2.5)的作用,以及1 μg/mL - 1 mg/mL岩藻多糖对两种细胞系(OMM1、OMM2.3)的作用。通过WST - 1检测法研究细胞增殖和活力,通过伤口愈合(划痕)检测法研究细胞迁移。采用酶联免疫吸附测定法(ELISA)检测血管内皮生长因子(VEGF)。通过与内皮细胞共培养评估血管生成。用过氧化氢诱导细胞毒性。采用蛋白质印迹法研究蛋白质表达(Akt、ERK1/2、Bcl - 2、Bax)。

结果

岩藻多糖在两种细胞系中增加了增殖,在一种细胞系中降低了增殖。在三种细胞系中迁移减少。岩藻多糖对VEGF的影响取决于细胞类型和浓度。在与92.1细胞的内皮共培养中,岩藻多糖显著增加了管状结构。此外,岩藻多糖显著保护所有测试的葡萄膜黑色素瘤细胞系免受过氧化氢诱导的细胞死亡。在氧化应激下,岩藻多糖未改变Bcl - 2、Bax或ERK1/2的表达,而在92.1细胞中诱导了Akt表达,但在其他任何细胞系中均未诱导。

结论

岩藻多糖未显示出抗肿瘤作用,但具有保护和促血管生成特性,这使得岩藻多糖不适宜作为治疗葡萄膜黑色素瘤的潜在新药。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7853/5532635/08db170250a8/marinedrugs-15-00193-g001.jpg

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