Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
Interuniversity Center of Marine Biology and Applied Ecology "G. Bacci" (CIBM), Viale N. Sauro 4, 57128 Livorno, Italy.
Mar Drugs. 2021 Oct 15;19(10):579. doi: 10.3390/md19100579.
Neuroblastoma (NB) is a common cancer in childhood, and lethal in its high-risk form, primarily because of its high metastatic potential. Targeting cancer cell migration, and thus preventing metastasis formation, is the rationale for more effective cancer therapy against NB. Previous studies have described the leaf extract from marine plant (POE) as an antioxidant, anti-inflammatory agent and inhibitor of cancer cell migration. This study aims to examine the POE anti-migratory role in human SH-SY5Y neuroblastoma cells and the underlying mechanisms of action. Wound healing and gelatin zymography assays showed that POE at early times inhibits cell migration and reduces pro-MMP-2 release into culture medium. By monitoring expression level of key autophagy markers by Western blot assay, a correlation between POE-induced cell migration inhibition and autophagy activation was demonstrated. Cell morphology and immunofluorescence analyses showed that POE induces neurite formation and neuronal differentiation at later times. These results suggest POE might act against cell migration by triggering early nontoxic autophagy. The POE-induced cellular morphological change toward cell differentiation might contribute to prolonging the phytocomplex anti-migratory effect to later times. Overall, these results encourage future in vivo studies to test POE applicability in neuroblastoma treatment.
神经母细胞瘤（NB）是一种常见的儿童癌症，其高危形式是致命的，主要是因为其高转移潜能。针对癌细胞迁移，从而防止转移形成，是针对 NB 进行更有效癌症治疗的基本原理。先前的研究已经描述了海洋植物（POE）的叶提取物具有抗氧化、抗炎作用和抑制癌细胞迁移的作用。本研究旨在研究 POE 在人 SH-SY5Y 神经母细胞瘤细胞中的抗迁移作用及其作用机制。伤口愈合和明胶酶谱分析表明，POE 在早期抑制细胞迁移并减少前 MMP-2 释放到培养基中。通过 Western blot 检测关键自噬标志物的表达水平，证明了 POE 诱导的细胞迁移抑制与自噬激活之间存在相关性。细胞形态和免疫荧光分析表明，POE 在后期诱导神经元突起形成和神经元分化。这些结果表明，POE 可能通过触发早期非毒性自噬来对抗细胞迁移。POE 诱导的细胞形态向细胞分化的变化可能有助于延长植物复合物的抗迁移作用到后期。总的来说，这些结果鼓励未来进行体内研究，以测试 POE 在神经母细胞瘤治疗中的适用性。
