Abstract:OBJECTIVE: The aim of this study was to investigate whether the induction of caspase-8 by γ-interferon (IFNγ) renders neuroblastoma (NB) cells sensitive to tumor necrosis factor related apoptosis inducing ligand(TRAIL). METHODS: Caspase-8 mRNA expression was determined by RT-PCR. The effects of IFNγ, TRAIL, IFNγ +TRAIL and caspase-8 inhibitor+ TRAIL on the growth and apoptosis of NB cells were detected with the methods of reduction rate of Alamar Blue assay and flow cytometry. The relative caspase-8 activity was measured with colorimetric assay. RESULTS: Caspase-8 expression was detectable in CHP212 cells which were sensitive to TRAIL, with an increased expression after treatment with IFNγ. Caspase-8 was undetectable in SH-SY5Y(SY5Y) cells which were resistant to TRAIL, but an increased expression of caspase-8 mRNA was found after treatment with IFNγ. Moreover, TRAIL combined with IFNγ induced apoptosis in SY5Y cells. The relative caspase-8 activity of CHP212 cells increased with the prolonged TRAIL action time. The relative caspase-8 activity of SY5Y cells in the IFNγ+TRAIL group was significantly higher than those of the control, IFNγ, TRAIL and inhibitor groups. CONCLUSIONS: NB cells expressing caspase-8 are sensitive to TRAIL. TRAIL induces apoptosis in NB cells with an increase of relative caspase-8 activity.[Chin J Contemp Pediatr, 2010, 12 (11):902-907]
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