Osteosarcoma is a bone tumor that mainly affects children and adolescents. Interferons (IFNs) have been shown to exert antitumor effects in osteosarcoma cells, although the molecular mechanisms have not been fully realized. We investigated IFN-γ actions on osteosarcoma cells. Our results show that IFN-γ induces the accumulation of autophagosomes in osteosarcoma cells. IFN-γ treatment leads to the conversion of autophagy marker light chain 3 (LC3)-I to LC3-II in osteosarcoma cells, and this conversion is accompanied by puncta formation. Also, IFN-γ–mediated induction of autophagosome formation and autophagic flux require RNA-dependent protein kinase (PKR) activity. In addition, our findings show that IFN-γ–mediated osteosarcoma cell death is not dependent on PKR. Our study suggests that IFN-γ has differential effects that lead to induction of cell death and autophagy in osteosarcoma cells. Further evaluation of the IFN-γ–mediated molecular mechanism could lead to improved understanding of and targeted treatment strategies for osteosarcoma.
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