Resistance to Gemcitabine (GEM) is a crucial problem in treatment of pancreatic cancer. Many studies indicate the direct impact of glycolytic enzyme on chemoresistance. However, it still has not been known whether Enolase 1 (ENO1), a multifunctional glycolytic enzyme, is a potential target to overcome GEM resistance in pancreatic ductal adenocarcinoma (PDAC). In this study, we showed that ENO1 high expression was associated with poor prognosis of PDAC patients. Moreover, we investigated the impacts of ENO1 silencing on hypoxia induced GEM chemoresistance in CFPAC-1 and MiaPaCa-2 cells. The results showed that, targeting ENO1 using ENO1-shRNA could sensitize hypoxia induced chemoresistance in pancreatic cancer cells by modulation of redox homeostasis, the mechanisms appear to be associated with influences on proliferation, apoptosis, and cell cycle regulated by increased intracellular reactive oxygen species (ROS). We demonstrated that targeting ENO1 could be a potential strategy for overcoming hypoxia induced GEM chemoresistance in PDAC cells.
Keywords: Phosphopyruvate hydratase; chemoresistance; gemcitabine; pancreatic neoplasms; redox homeostasis.