Differential response of neuroblastoma cells to TRAIL is independent of PI3K/AKT

Academic Article

Abstract

  • Background: In many human tumor cells, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis through caspase activation, whereas activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway prevents apoptosis. We hypothesized that inhibition of PI3K/Akt would increase TRAIL-induced apoptosis in neuroblastoma cells. Methods: SK-N-AS, SH-SY5Y, and IMR-32 neuroblastoma cells were cultured with either standard media or media with PI3K/Akt inhibitor for 24 hours. These cells were then exposed to 100 ng/mL of TRAIL for 90 minutes and harvested. Cells either underwent flow cytometric analysis of apoptosis, had protein extracted for Western blot, had RNA extracted for reverse transcription-polymerase chain reaction, or had cell lysates analyzed for caspase-3, -8, and -9. Results: Baseline expression of TRAIL receptors and Akt varied among the cell lines. Inhibition of PI3K/Akt decreased caspase-3 activation in the AS and SY cells, but did not alter TRAIL-induced apoptosis in any of the cell lines. Activity of caspase-8 and -9 was also unaffected by PI3K/Akt attenuation. Conclusions: Inhibition of the PI3K/Akt pathway does not increase the sensitivity of neuroblastoma cell lines to TRAIL-induced apoptosis. Neuroblastoma is unique in that activation of the PI3K/Akt pathway is either not essential to its TRAIL resistance or counteracted because of the multiple repetitive pathways of TRAIL resistance. © 2006 Elsevier Inc. All rights reserved.
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    Digital Object Identifier (doi)

    Author List

  • Efron PA; Chen MK; Iyengar M; Dai W; Nagaram A; Beierle EA
  • Start Page

  • 1072
  • End Page

  • 1080
  • Volume

  • 41
  • Issue

  • 6