Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan, Republic of Korea.
Int Immunopharmacol. 2011 Dec;11(12):2208-13. doi: 10.1016/j.intimp.2011.10.002. Epub 2011 Oct 18.
Melanoma is an aggressive form of skin cancer due to its rapid metastasis. Recently, several studies have reported that selenium can prevent metastasis of melanoma cells, but the mechanism of this anti-metastatic ability is not fully understood. In this study, we investigated the effect of selenium on cell migration in melanoma and on tumor metastasis in mice. Interestingly, tumor metastasis was suppressed by selenium in a mouse model. Cell migration was measured by a wound-healing assay using selenium-treated melanoma cells. Treatment with a non-cytotoxic concentration of selenium suppressed migration of melanoma cells in a dose-dependent manner. In addition, we found decreased HIF-1α and VEGF expression in selenium-treated melanoma cells as compared to non-treated control cells. Mechanistically, our studies show that selenium inhibits IL-18 gene expression in a dose-dependent manner. IL-18 protein level was suppressed by treatment with selenium. The wound-healing assay revealed that the anti-metastatic effect of selenium was abrogated by treatment with exogenous IL-18. These results suggest that selenium might be a potent inhibitor of the metastatic capacity of melanoma cells, via down-modulation of IL-18 expression.
黑色素瘤是一种侵袭性皮肤癌，因其快速转移而备受关注。最近，有几项研究报道称，硒可以预防黑色素瘤细胞的转移，但这种抗转移能力的机制尚未完全阐明。在这项研究中，我们研究了硒对黑色素瘤细胞迁移和小鼠肿瘤转移的影响。有趣的是，硒在小鼠模型中抑制了肿瘤转移。我们使用硒处理的黑色素瘤细胞进行划痕实验来测量细胞迁移。非细胞毒性浓度的硒处理以剂量依赖的方式抑制黑色素瘤细胞的迁移。此外，我们发现与未经处理的对照细胞相比，硒处理的黑色素瘤细胞中 HIF-1α 和 VEGF 的表达减少。从机制上讲，我们的研究表明，硒以剂量依赖的方式抑制 IL-18 基因的表达。用硒处理后，IL-18 蛋白水平受到抑制。划痕实验表明，外源性 IL-18 处理可消除硒的抗转移作用。这些结果表明，硒可能通过下调 IL-18 的表达，成为黑色素瘤细胞转移能力的有效抑制剂。
