PomGnT1 enhances temozolomide resistance by activating epithelial-mesenchymal transition signaling in glioblastoma
PomGnT1 enhances temozolomide resistance by activating epithelial-mesenchymal transition signaling in glioblastoma
复制标题
PomGnT1 通过激活胶质母细胞瘤中的上皮间质转化信号增强替莫唑胺耐药性
DOI：
10.3892/or.2017.5964
复制
发表时间：
2017-11-01
期刊：
影响因子：
4.2
通讯作者：
Lan, Jin
中科院分区：
文献类型：
--
作者：
Liu, Qi;Xue, Yajun;Lan, Jin
替莫唑胺（TMZ）常用于胶质母细胞瘤（GBM）化疗。然而，TMZ治疗的一个巨大挑战是耐药性的快速发展和随后的肿瘤复发和不良结局。在本研究中，我们建立了TMZ耐药GBM细胞（U87-TR和U251-TR），发现与TMZ敏感的对应物相比，PomGnT 1的表达在TMZ耐药GBM细胞中显著上调。此外，PomGnT 1在U87-MG和U251-MG细胞中的过表达导致TMZ的IC 50值增加和细胞凋亡减少。在U87-TR和U251-TR细胞中敲低PomGnT 1导致TMZ的IC 50值降低和细胞凋亡增加。生化分析显示，PomGnT 1调节GBM细胞中上皮-间质转化信号传导中的因子的表达，包括TCF 8、波形蛋白、β-连环蛋白和Slug。这些发现表明，PomGnT 1可能是GBM研究的新焦点，用于治疗复发性TMZ耐药GBM。
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, beta-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.