PomGnT1 enhances temozolomide resistance by activating epithelial-mesenchymal transition signaling in glioblastoma

Liu,Qi; Xue,Yajun; Chen,Qingshan; Chen,Huairui; Zhang,Xiaofei; Wang,Leiping; Han,Cong; Que,Shuanglin; Lou,Meiqing; Lan,Jin

doi:10.3892/or.2017.5964

PomGnT1 enhances temozolomide resistance by activating epithelial-mesenchymal transition signaling in glioblastoma

Authors:
- Qi Liu
- Yajun Xue
- Qingshan Chen
- Huairui Chen
- Xiaofei Zhang
- Leiping Wang
- Cong Han
- Shuanglin Que
- Meiqing Lou
- Jin Lan
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Affiliations: Department of Neurosurgery, Jingdezhen Second Hospital, Jingdezhen, Jiangxi, P.R. China, Department of Neurosurgery, General Hospital, Shanghai, P.R. China, Department of Neurosurgery, The Second People's Hospital of Liaocheng City, Liaocheng, Shandong, P.R. China, Department of Neurosurgery, Longyan First Hospital, Fujian Medical University, Longyan, Fujian, P.R. China, Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China
Published online on: September 19, 2017 https://doi.org/10.3892/or.2017.5964
Pages: 2911-2918

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Abstract

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.

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