Abstract

Tumor cells preferentially use anaerobic glycolysis rather than oxidative phosphorylation to generate energy. Hexokinase II (HK-II) is necessary for anaerobic glycolysis and displays aberrant expression in malignant cells. The current study aimed to evaluate the role of HK-II in the survival and biological function of nasopharyngeal carcinoma (NPC). Our study demonstrated that high expression of HK-II was associated with poor survival outcomes in NPC patients. When using 3-BrOP (an HK-II inhibitor) to repress glycolysis, cell proliferation and invasion were attenuated, accompanied by the induction of apoptosis and cell cycle arrest at the G1 stage. Furthermore, 3-BrOP synergized with cisplatin (DDP) to induce NPC cell death. Collectively, we provided that the aberrant expression of HK-II was associated with the malignant phenotype of NPC. A combined treatment modality that targets glycolysis with DDP holds promise for the treatment of NPC patients.

Highlights

  • Nasopharyngeal carcinoma (NPC) is a malignancy that originates from the nasopharyngeal epithelium

  • We found a small increase in NPC cell sensitivity to 3-bromo-2-oxopropionate-1-propyl ester (3-BrOP) under hypoxic conditions compared to normoxic conditions

  • We found that high expression levels of Hexokinase II (HK-II) were correlated with poor prognosis, including worse loco-regional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) compared with low expression levels of HK-II

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Summary

Introduction

Nasopharyngeal carcinoma (NPC) is a malignancy that originates from the nasopharyngeal epithelium. In most of the world, the incidence rate is lower than 1 in 100,000. Despite intensive radiotherapy and chemotherapy, 8.4–10.9% of patients still experience tumor recurrence [4, 5] , and 15–42% of patients with NPC face distant metastasis after initial treatment [6, 7]. These findings indicate the need for further understanding of the etiology and pathogenesis of this disease

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