Long-term prognostic implications and therapeutic target role of hexokinase II in patients with nasopharyngeal carcinoma

// Meng-Xia Zhang 1, 2, * , Yi-Jun Hua 1, 2, * , Hai-Yun Wang 1, 3 , Ling Zhou 1 , Hai-Qiang Mai 1, 2 , Xiang Guo 1, 2 , Chong Zhao 1, 4 , Wen-Lin Huang 1 , Ming-Huang Hong 1, 2 , Ming-Yuan Chen 1, 2 1 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China 2 Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China 3 Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China 4 Department of Radiotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China * These authors have contributed equally to this work Correspondence to: Ming-Yuan Chen, e-mail: chmingy@mail.sysu.edu.cn Ming-Huang Hong, e-mail: hongmh@sysucc.org.cn 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 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.