RNA interference targeting Akt promotes apoptosis in hypoxia-exposed human neuroblastoma cells.
Overactivation of the PI3 kinase/Akt pathway plays an essential role in the development and progression of various tumors. Akt is a key component of this pathway and hyperactivated in different tumors including neuroblastoma and glioma. In the present study, we tested the therapeutic efficacy of siRNA targeting Akt in inducing apoptotic cell death in NBFL cells (a human neuroblastoma cell line) subjected to anoxia/reoxygenation (A/R), a process that has been shown to modulate growth and progression of malignant tumors. We observed that siRNA targeting Akt effectively induced apoptotic cell death in NBFL cells (as determined by TUNEL assay and activated caspase-3 immunoreactivity) under normoxic conditions, an effect that was greatly enhanced under conditions of A/R. These findings underscore the importance of Akt signaling in promoting survival of neuroblastoma cells and may have potential therapeutic applications.
Liu
Xiu-Huai
XH
Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA. liuxiuhuai@mail.nih.gov
Yu
Erik Z
EZ
Li
Ying-Yue
YY
Rollwagen
Florence M
FM
Kagan
Elliott
E
D017209:Apoptosis; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010100:Oxygen / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D015854:Up-Regulation
D051057:Proto-Oncogene Proteins c-akt; D010100:Oxygen