文章：

半胱胺通过抑制基质金属蛋白酶活性抑制胶质母细胞瘤中癌细胞的侵袭和迁移

Cysteamine Suppresses Cancer Cell Invasion and Migration in Glioblastoma through Inhibition of Matrix Metalloproteinase Activity

原文发布日期：27 May 2024

DOI: 10.3390/cancers16112029

类型: Article

开放获取: 是

英文摘要：

Glioblastoma (GBM) cells are highly invasive, infiltrating the surrounding normal brain tissue, thereby limiting the efficacy of surgical resection and focal radiotherapy. Cysteamine, a small aminothiol molecule that is orally bioavailable and approved for cystinosis, has potential as a cancer treatment by inhibiting tumor cell invasion and metastasis. Here we demonstrate that these potential therapeutic effects of cysteamine are likely due to the inhibition of matrix metalloproteinases (MMPs) in GBM. In vitro assays confirmed that micromolar concentrations of cysteamine were not cytotoxic, enabling the interrogation of the cellular effects without confounding tumor cell loss. Cysteamine’s inhibition of MMP activity, especially the targeting of MMP2, MMP9, and MMP14, was observed at micromolar concentrations, suggesting the mechanism of action in suppressing invasion and cell migration is by inhibition of these MMPs. These findings suggest that achievable micromolar concentrations of cysteamine effectively inhibit cancer cell invasion and migration in GBM, supporting the potential for use as an adjunct cancer treatment.

摘要翻译： 

胶质母细胞瘤细胞具有高度侵袭性，可浸润周围正常脑组织，从而限制手术切除和局部放疗的疗效。半胱胺是一种口服生物可利用的小分子氨基硫醇类药物，已获批用于胱氨酸贮积症治疗，通过抑制肿瘤细胞侵袭和转移而具有癌症治疗潜力。本研究证实半胱胺的这种潜在治疗效应可能源于其对胶质母细胞瘤中基质金属蛋白酶的抑制作用。体外实验证实微摩尔浓度半胱胺无细胞毒性，可在排除肿瘤细胞损失干扰的前提下探究其细胞效应。在微摩尔浓度下观察到半胱胺对基质金属蛋白酶活性的抑制，特别是对MMP2、MMP9和MMP14的靶向作用，表明其抑制侵袭和细胞迁移的作用机制是通过抑制这些基质金属蛋白酶实现的。这些发现表明，可达到的微摩尔浓度半胱胺能有效抑制胶质母细胞瘤的癌细胞侵袭和迁移，支持其作为辅助癌症治疗的潜在应用价值。

原文链接：

Cysteamine Suppresses Cancer Cell Invasion and Migration in Glioblastoma through Inhibition of Matrix Metalloproteinase Activity