RESUMO
Hypoxia, as an important hallmark of the tumor microenvironment, is a major cause of oxidative stress and plays a central role in various malignant tumors, including glioblastoma. Elevated reactive oxygen species (ROS) in a hypoxic microenvironment promote glioblastoma progression; however, the underlying mechanism has not been clarified. Herein, we found that hypoxia promoted ROS production, and the proliferation, migration, and invasion of glioblastoma cells, while this promotion was restrained by ROS scavengers N-acetyl-L-cysteine (NAC) and diphenyleneiodonium chloride (DPI). Hypoxia-induced ROS activated hypoxia-inducible factor-1α (HIF-1α) signaling, which enhanced cell migration and invasion by epithelial-mesenchymal transition (EMT). Furthermore, the induction of serine protease inhibitor family E member 1 (SERPINE1) was ROS-dependent under hypoxia, and HIF-1α mediated SERPINE1 increase induced by ROS via binding to the SERPINE1 promoter region, thereby facilitating glioblastoma migration and invasion. Taken together, our data revealed that hypoxia-induced ROS reinforce the hypoxic adaptation of glioblastoma by driving the HIF-1α-SERPINE1 signaling pathway, and that targeting ROS may be a promising therapeutic strategy for glioblastoma.
Assuntos
Humanos , Hipóxia Celular , Linhagem Celular Tumoral , Glioblastoma/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Microambiente Tumoral , Neoplasias Encefálicas/patologiaRESUMO
Objective To investigate the reason for hidden hemorrhage of hip fracture in elder.Methods All of 94 elder patients,who were diagnosed with intertrochanteric fracture or femoral neck fracture and received treatment in our department from October,2013 to September,2015,were included in this study.The time between injuries to admission was less than 4 hours of the two groups of patients.And the patients whose hemoglobin was less than 100 g/L were removed when admission,in order to avoid the interference of primary anemia.All information,including height,weight,and the value of hemoglobin (Hb) and hematocrit (Hct),were collected.Blood tests were performed immediately after admission,at daily morning preoperatively,and at the morning of the day of surgery.Preoperative blood loss (hidden hemorrhage) was recorded.With respect to blood loss of hidden hemorrhage,statistical analysis was performed at different times (immediate time after admission,and day 1,2,and 3 postoperatively)in the group of intertrochanteric fracture or in the group of femoral neck fracture,and subsequently performed between the two groups.Results The blood loss in the group of intertrochanteric fracture was 196.3 ml,310.1 ml and 418.3 ml in the 1st day,the 2nd day and the third day after admission.There was a significant difference among different time with respect to blood loss.The blood loss was 39.8 ml,65.7 ml and 82.9 ml in the 1st day,the 2nd day and the third day after admission in the group of femoral neck fracture.There was also a significant difference among different time with respect to blood loss.In experimental group,mean blood loss was 418.3 ml and mean Hb decreased by 23.7 g/L at day 3 postoperatively.In control group,mean blood loss was 82.9 ml and mean Hb decreased by 6.7 g/L at day 3 postoperatively.A significant difference was observed between the two groups.The blood loss in patients with intertrochanteric fracture was higher than that in patients with femoral neck fracture.Conclusion The blood loss was gradually increased in elder patients with intertrochanteric fracture over time.There was a significant difference in different time with respect to blood loss.Moreover,a significant difference was found in blood loss of hidden hemorrhage between intertrochanteric fracture and femoral neck fracture.