title: Radiosensitisation of human glioma cells by inhibition of β1,6-GlcNAc branched N-glycans.
abstract: 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.
authors.affiliation: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan, 442000, Hubei, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, Hubei University of Medicine, 30 South Renmin Road, Shiyan, 442000, Hubei, People's Republic of China.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Dong
authors.affiliation: Center for Evidence-based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan, 442000, People's Republic of China.
authors.forename: Jun-Bo
authors.initials: JB
authors.lastname: Wu
authors.affiliation: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan, 442000, Hubei, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan, 442000, Hubei, People's Republic of China.
authors.forename: Qi-Wen
authors.initials: QW
authors.lastname: Duan
authors.affiliation: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan, 442000, Hubei, People's Republic of China. zhiguo_luo@163.com.
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Luo
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D011134:Polysaccharides / Q000096:biosynthesis* / Q000235:genetics; D011827:Radiation; D011836:Radiation Tolerance / Q000235:genetics*; D014410:Tumor Stem Cell Assay; D014415:Tunicamycin / Q000008:administration & dosage
chemical_list: D011134:Polysaccharides; D014415:Tunicamycin; C000601122:Mgat5 protein, human; D017351:N-Acetylglucosaminyltransferases
keywords: Glioma; GnT-V; Radiosensitivity; β1,6-GlcNAc branched N-glycans