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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Apoptosis, Apoptosis Regulatory Proteins, Caspase 3, Caspase 8, Caspase 9, Caspases, Cell Line, Tumor, Chromones, Enzyme Activation, Enzyme Inhibitors, Humans, Membrane Glycoproteins, Morpholines, Neuroblastoma, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, RNA, Messenger, Receptors, Tumor Necrosis Factor, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor-alpha.
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Is differential response of neuroblastoma cells to TRAIL independent of PI3K/AKT? Context: 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. 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. 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.
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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. Final Decision: yes