Department of Neurosurgery, Jingdezhen Second Hospital, Jingdezhen, Jiangxi, P.R. China.
Department of Neurosurgery, General Hospital, Shanghai, P.R. China.
Oncol Rep. 2017 Nov;38(5):2911-2918. doi: 10.3892/or.2017.5964. Epub 2017 Sep 19.
Temozolomide (TMZ) is commonly used in glioblastoma (GBM) chemotherapy. However, a great challenge for TMZ treatment is the rapid development of resistance and subsequent tumor recurrence and poor outcome. In the present study we established TMZ-resistant GBM cells (U87-TR and U251-TR) and found that the expression of PomGnT1 was significantly upregulated in TMZ-resistant GBM cells compared with the TMZ-sensitive counterparts. Furthermore, overexpression of PomGnT1 in U87-MG and U251-MG cells led to increased IC50 values for TMZ and reduced apoptosis of cells. Knockdown of PomGnT1 in both U87-TR and U251-TR cells led to decreased IC50 values for TMZ and enhanced apoptosis. Biochemical analysis revealed that PomGnT1 regulates the expression of factors in epithelial-mesenchymal transition signaling including TCF8, vimentin, β-catenin and Slug in GBM cells. These findings demonstrate that PomGnT1 might be a new focus of GBM research for treatment of recurrent TMZ-resistant GBM.
替莫唑胺（TMZ）常用于胶质母细胞瘤（GBM）的化疗。然而，TMZ 治疗的一个巨大挑战是耐药性的迅速发展，以及随后的肿瘤复发和不良预后。在本研究中，我们建立了 TMZ 耐药性 GBM 细胞（U87-TR 和 U251-TR），并发现与 TMZ 敏感细胞相比，TMZ 耐药性 GBM 细胞中 PomGnT1 的表达显著上调。此外，在 U87-MG 和 U251-MG 细胞中过表达 PomGnT1 导致 TMZ 的 IC50 值增加，细胞凋亡减少。在 U87-TR 和 U251-TR 细胞中敲低 PomGnT1 导致 TMZ 的 IC50 值降低，细胞凋亡增强。生化分析表明，PomGnT1 调节 GBM 细胞中上皮-间充质转化信号转导中因子的表达，包括 TCF8、波形蛋白、β-连环蛋白和 Slug。这些发现表明 PomGnT1 可能是治疗复发性 TMZ 耐药性 GBM 的新的研究焦点。
