PDF(Pubmed)
Abstract：
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：
胶质母细胞瘤（GBM）细胞具有高度侵袭性，浸润周围的正常脑组织,从而限制了手术切除和局灶性放疗的疗效。半胱胺,一种小的氨基硫醇分子，是口服生物可利用的，被批准用于胱氨酸病，通过抑制肿瘤细胞的侵袭和转移，具有作为癌症治疗的潜力。在这里，我们证明半胱胺的这些潜在治疗作用可能是由于GBM中基质金属蛋白酶（MMPs）的抑制。体外试验证实，微摩尔浓度的半胱胺没有细胞毒性，能够在不混淆肿瘤细胞损失的情况下询问细胞效应。半胱胺对MMP活性的抑制作用，特别是在微摩尔浓度下观察到MMP2，MMP9和MMP14的靶向，提示抑制侵袭和细胞迁移的作用机制是通过抑制这些MMP。这些发现表明，可实现的微摩尔浓度的半胱胺有效抑制GBM中的癌细胞侵袭和迁移，支持用作辅助癌症治疗的潜力。
