N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. In this study, we used GnT-V as a molecular target to further sensitize cetuximab-treated NPC cells to radiation. The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. GnT-V down-regulation combined with cetuximab decreased the survival fraction, healing rate and cell viability and increased the apoptosis rate. Concomitantly, the combination of cetuximab and irradiation did not change the EGFR mRNA and protein levels and decreased the β-1-6 branching on the EGFR. Subsequently, we further explored the signaling downstream of EGF, particularly the PI3K/Akt signaling pathway, and discovered that treatment consisting of GnT-V down-regulation, irradiation and cetuximab was negatively correlated with phospho-Akt and phspho-PI3K. Finally, an in vivo experiment with radiotherapy revealed that the combination of GnT-V down-regulation and cetuximab decelerated tumor growth. In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC radiosensitivity, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR.

中文翻译：

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抑制N-乙酰氨基葡萄糖氨基转移酶V可增强西妥昔单抗诱导的鼻咽癌细胞的放射敏感性，可能是通过EGFR N-聚糖改变

ñ催化寡糖N-连接的β-1-6分支形成的酶-乙酰氨基葡萄糖氨基转移酶V（GnT-V）与鼻咽癌（NPC）的放射敏感性有关。西妥昔单抗（C225）是一种表皮生长因子受体（EGFR）抑制剂，在NPC的治疗中用作放射增敏剂。在这项研究中，我们使用GnT-V作为分子靶标，以进一步使西妥昔单抗治疗的NPC细胞对放射线敏感。两种NPC细胞系（CNE1和CNE2）的结果表明，沉默GnT-V可通过减少EGFR上寡糖的β-1-6分支来增强西妥昔单抗诱导的放射敏感性。GnT-V下调联合西妥昔单抗降低了存活率，治愈率和细胞活力并增加了细胞凋亡率。同时，西妥昔单抗联合放疗不会改变EGFR mRNA和蛋白水平，并减少了EGFR上的β-1-6分支。随后，我们进一步探索了EGF的下游信号传导，特别是PI3K / Akt信号传导通路，并发现由GnT-V下调，辐射和西妥昔单抗组成的治疗与磷酸化Akt和phspho-PI3K负相关。最后，放射疗法的体内实验表明，GnT-V下调和西妥昔单抗的组合可减缓肿瘤的生长。总之，我们的研究表明，降低的GnT-V活性和西妥昔单抗的组合可增强NPC的放射敏感性，而这种作用的潜在机制可能涉及EGFR的N-联β1-6分支。