Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand.
Cell Mol Neurobiol. 2018 Mar;38(2):559-573. doi: 10.1007/s10571-017-0507-z. Epub 2017 Jun 9.
Glioblastoma is one of the most malignant and aggressive types of brain tumors. 5-lipoxygenase and cysteinyl leukotriene receptor 1 (CysLT1) play a role in human carcinogenesis. Leukotriene receptor antagonists (LTRAs), anti-asthmatic drugs with mild side effects, have anti-metastatic activity in epidermoid carcinoma, lung carcinoma, and colon cancers as well as neuroprotective effects. Herein, anti-migratory effects of two LTRAs, montelukast and zafirlukast, were investigated in glioblastoma cells. The level of CysLT1 in A172 cells was increased by 3.13 folds after IL-1β treatment. The median toxic concentration of LTRAs in A172, U373, and primary astrocytes ranged from 7.17 to 26.28 μM at 24-h post-exposure. Both LTRAs inhibited migration and invasion of glioma. Additionally, both drugs significantly inhibited the expression and activities of MMP-2 and MMP-9 in A172 and U373 glioblastoma cells and primary human astrocytes, suggesting that CysLT1 plays a role in migration and invasion of glioma, and LTRAs are potential drugs to reduce migration and invasion.
胶质母细胞瘤是最恶性和侵袭性的脑肿瘤之一。5-脂氧合酶和半胱氨酰白三烯受体 1（CysLT1）在人类肿瘤发生中起作用。白三烯受体拮抗剂（LTRA）是一种副作用较小的抗哮喘药物，在表皮样癌、肺癌、结肠癌以及神经保护方面具有抗转移活性。在此，研究了两种 LTRA（孟鲁司特和扎鲁司特）对胶质母细胞瘤细胞的迁移抑制作用。IL-1β处理后 A172 细胞中的 CysLT1 水平增加了 3.13 倍。在暴露后 24 小时，LTRA 在 A172、U373 和原代星形胶质细胞中的半数毒性浓度范围为 7.17 至 26.28 μM。两种 LTRA 均抑制胶质瘤的迁移和侵袭。此外，两种药物均显著抑制 A172 和 U373 胶质母细胞瘤细胞以及原代人星形胶质细胞中 MMP-2 和 MMP-9 的表达和活性，表明 CysLT1 参与了胶质瘤的迁移和侵袭，LTRA 可能是减少迁移和侵袭的潜在药物。
