Targeting PI3K/Akt represses Hypoxia inducible factor-1 alpha activation and sensitizes Rhabdomyosarcoma and Ewing's sarcoma cells for apoptosis

Background: Hypoxia inducible factor-1 alpha (HIF-1 alpha) has been identified as an important novel target in apoptosis resistance of pediatric tumors such as Rhabdomyosarcoma (RMS) and Ewing's sarcoma (ES). Evidence suggests that PI3K/Akt signaling plays a role in regulation of HIF-1 alpha activation as well as apoptosis resistance in various adult tumors. However the relevance of PI3K/Akt signaling in HIF-1b alpha activation and apoptosis resistance in childhood tumors has not been addressed yet. Thus, this study was to investigate whether PI3K/Akt signaling is involved in hypoxia induced activation of HIF-1 alpha as well as in resistance to hypoxia-induced apoptosis in childhood tumors such as RMS and ES.