Hypoxia Induced by Cobalt Chloride Triggers Autophagic Apoptosis of Human and Mouse Drug-Resistant Glioblastoma Cells through Targeting the PI3K-AKT-mTOR Signaling Pathway

Figure 8

Proposed signal-transducing pathways of hypoxia-induced autophagy and subsequently apoptotic killing of human drug-resistant glioblastoma cells. Treatment of human TMZ-resistant glioblastoma cells with CoCl₂ induces hypoxic insults by suppressing phosphoinositide 3-kinase- (PI3K-) involved signal-transducing phosphorylations of AKT and mammalian target of rapamycin (mTOR). Consequently, long-period administration of CoCl₂ induced cascade activation of caspases-3 and -6, DNA breakage, and apoptotic insults to human drug-resistant glioblastoma cells.