Gliomas are the most prevalent type of primary brain tumors and are resistant to radiation therapy. β1,6-GlcNAc branched N-glycans, which are encoded by N-acetylglucosaminyltransferase V (GnT-V), play important roles in glioma progression. However, the relationship between β1,6-GlcNAc branched expression and radiosensitivity in glioma cells is still unknown. In this study, the expression of β1,6-GlcNAc branched N-glycans in nonneoplastic brain and glioma samples was characterized by lectin histochemistry. The radiosensitivity of glioma cells was evaluated by colony formation assay. We found that β1,6-GlcNAc branches were highly expressed in glioblastoma specimens, compared with diffuse astrocytomas and nonneoplastic brain. In addition, β1,6-GlcNAc branched expression was negatively correlated with the radiosensitivity of glioblastoma cells. Furthermore, the inhibition of N-linked β1,6-GlcNAc branches by GnT-V silencing in U251 cells could reduce the cell clonogenic survival after X-irradiation. Meanwhile, the G2/M checkpoint was impaired and there was an increase in the number of apoptotic cells. Tunicamycin, an inhibitor of N-glycan biosynthesis, was also able to enhance the radiosensitivity of U251 cells. Thus, our results suggest that development of therapeutic approaches targeting N-linked β1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment.
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This study was supported by grants from the Foundation for Innovative Research Team of Hubei University of Medicine (2014CXG02), the Key Discipline Project of Hubei Province (2014XKJSXJ12), and the Scientific and Technological Project of Shiyan City of Hubei Province (15K65).
Compliance of ethical standards
Informed consent was obtained from all patients enrolled in this study, and the study protocol was approved by the Ethics Committee of Hubei University of Medicine.
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