Article Abstract

Downregulation of hexokinase 2 improves radiosensitivity of breast cancer

Authors: Dan Zhang, Hui Wang, Wenjing Yu, Feng Qiao, Xiaoyu Su, Huiqin Xu


Background: Hexokinase 2 (HK2) is a major glycolytic enzyme that plays a critical role in the development of tumor metabolism. Triple negative breast cancers (TNBC) have high glycolytic activity and poor prognosis. This study explored the effect of HK2 on radiotherapy (RT) sensitivity of TNBC.
Methods: The knockdown of HK2 genes in TNBC by lentiviral shRNA was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. In addition, the boosts of radiation therapy effects of TNBC accompanied by a reduction of HK2 gene were determined by CCK-8, flow cytometry and colonic formation assays. (18F)-fluorodeoxyglucose (18F-FDG) uptake was used to evaluate tumor growth before and after radiation therapy in vivo.
Results: After administration of lentiviral shHK2, the expressions of HK2 proteins and mRNA were inhibited effectively. Following exposure to different doses of X-rays, the survival rate of cells and colony formation displayed a decreased trend and the cell apoptosis rate increased in the Lv-shHK2 group (P<0.05). In addition, (18F)-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging showed that compared with control, the maximum standardized uptake value (SUVmax) was lower in the Lv-shHK2 group.
Conclusions: Downregulation of HK2 improved the radiosensitivity of breast cancer (BC).