Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei 10581, Taiwan.
Sensors (Basel). 2019 May 16;19(10):2275. doi: 10.3390/s19102275.
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. In recent studies, the efficacy of suberoylanilide hydroxamic acid (SAHA) has been investigated for GBM. We explored the effects of two exploratory compounds, the histone deacetylase SAHA and the natural product andrographolide, on Uppsala 87 Malignant Glioma (U-87 MG) cell migration and viability in comparison with the clinically used therapeutic agent temozolomide (TMZ). We used the electric cell-substrate impedance sensing (ECIS) system to monitor the migration of U-87 MG cells after treatment with various concentrations of these compounds. Moreover, we used the Alamar blue assay and western blotting to observe the concentration-dependent changes in the viability and apoptosis of U-87 MG cells. Our results demonstrated that both SAHA and andrographolide (10-300 μM) significantly inhibited GBM cell migration in a concentration-dependent manner, and 10 μM SAHA and 56 μM andrographolide demonstrated remarkable inhibitory effects on U-87 MG migration. Western blotting indicated that compared with TMZ, both SAHA and andrographolide induced higher expression levels of apoptosis-related proteins, such as caspase-3, BAX, and PARP in U-87 MG cells. Furthermore, all three drugs downregulated the expression of the antiapoptotic protein Bcl-2. In conclusion, SAHA and andrographolide showed exceptional results in inhibiting cell migration and motility. The ECIS wound healing assay is a powerful technique to identify and screen potential therapeutic agents that can inhibit cancer cell migration.
多形性胶质母细胞瘤（GBM）是成人中最常见和侵袭性最强的原发性脑肿瘤。在最近的研究中，已研究了琥珀酰亚胺基羟肟酸（SAHA）对 GBM 的疗效。我们探讨了两种探索性化合物，组蛋白去乙酰化酶 SAHA 和天然产物穿心莲内酯，对乌普萨拉 87 恶性神经胶质瘤（U-87 MG）细胞迁移和活力的影响，并与临床使用的治疗剂替莫唑胺（TMZ）进行了比较。我们使用细胞-基质阻抗感应（ECIS）系统监测这些化合物不同浓度处理后 U-87 MG 细胞的迁移。此外，我们使用 Alamar blue 测定法和 Western blot 观察 U-87 MG 细胞活力和凋亡的浓度依赖性变化。我们的结果表明，SAHA 和穿心莲内酯（10-300 μM）均以浓度依赖性方式显著抑制 GBM 细胞迁移，10 μM SAHA 和 56 μM 穿心莲内酯对 U-87 MG 迁移表现出显著的抑制作用。Western blot 表明，与 TMZ 相比，SAHA 和穿心莲内酯在 U-87 MG 细胞中诱导了更高水平的凋亡相关蛋白，如 caspase-3、BAX 和 PARP。此外，这三种药物均下调了抗凋亡蛋白 Bcl-2 的表达。总之，SAHA 和穿心莲内酯在抑制细胞迁移和运动方面表现出优异的效果。ECIS 划痕愈合试验是一种强大的技术，可以识别和筛选能够抑制癌细胞迁移的潜在治疗剂。
