Radiosensitisation of human glioma cells by inhibition of beta 1,6-GlcNAc branched N-glycans

摘要

Gliomas are the most prevalent type of primary brain tumors and are resistant to radiation therapy. beta 1,6-GlcNAc branched N-glycans, which are encoded by N-acetylglucosaminyltransferase V (GnT-V), play important roles in glioma progression. However, the relationship between beta 1,6-GlcNAc branched expression and radiosensitivity in glioma cells is still unknown. In this study, the expression of beta 1,6-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 beta 1,6-GlcNAc branches were highly expressed in glioblastoma specimens, compared with diffuse astrocytomas and nonneoplastic brain. In addition, beta 1,6-GlcNAc branched expression was negatively correlated with the radiosensitivity of glioblastoma cells. Furthermore, the inhibition of N-linked beta 1,6-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 beta 1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment.