Long-term prognostic implications and therapeutic target role of hexokinase II in patients with nasopharyngeal carcinoma
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Meng-Xia Zhang1,2,*, Yi-Jun Hua1,2,*, Hai-Yun Wang1,3, Ling Zhou1, Hai-Qiang Mai1,2, Xiang Guo1,2, Chong Zhao1,4, Wen-Lin Huang1, Ming-Huang Hong1,2, Ming-Yuan Chen1,2
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China
2Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
3Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
4Department of Radiotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
*These authors have contributed equally to this work
Ming-Yuan Chen, e-mail: [email protected]
Ming-Huang Hong, e-mail: [email protected]
Keywords: nasopharyngeal carcinoma (NPC), hexokinase II (HK-II), survival, 3-bromo-2-oxopropionate-1-propyl ester (3-BrOP), therapeutic target
Received: September 29, 2015 Accepted: January 18, 2016 Published: February 01, 2016
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.
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