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Updated: Jan 21, 2026
Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma
Published on: October 14, 2016
Interferon-γ Sensitises Human Osteosarcoma Cells to Trail-mediated Apoptosis
Idun M Mikkelsen1, Cecilie Løkke1, Trond Flagstad1,2
1Department of Paediatrics, Institute of Clinical Medicine, University of Tromsø, N-9037 Tromsø.
Background:
Nearly half of all patients with osteosarcoma are still not cured by the currently employed multimodal treatment. New strategies are therefore needed to further improve the outcome. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2) is able to induce programmed cell death in transformed cells, while normal cells remain unaffected.
Materials And Methods:
We have investigated the effect of TRAIL in combination with IFN-γ on four human osteosarcoma cell lines; Saos-2, U2OS, KPDXM and OHS, and on one normal human fibroblast cell line, MRC-5.
Results:
One of the four osteosarcoma cell lines was TRAIL-resistant, but was sensitised to TRAIL-mediated cell death upon pre-incubation with IFN-γ. In two of the three TRAIL-sensitive cell lines, the effect of TRAIL was enhanced by IFN-γ. The normal human fibroblast cell line MRC-5 was not affected by treatment with TRAIL and IFN-γ. A caspase cascade involving the activation of caspase-8, caspase-7 and PARP was associated with the onset of apoptosis in the osteosarcoma cell lines. Apoptosis was partly inhibited by the addition of caspase inhibitors zVADfmk (general inhibitor) and zIETDfmk (selective caspase-8 inhibitor). These findings further emphasize the important role of the caspases in cell death signalling.
Conclusion:
Our results show that treatment with both IFN-γ and TRAIL efficiently induces cell death in osteosarcoma cell lines and should be further investigated as a potential future therapy.
Insights
Combining Interferon-gamma (IFN-γ) with Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) effectively induces cancer cell death in osteosarcoma models. This combination therapy shows promise for improving patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Signaling
Background:
- Osteosarcoma treatment remains challenging, with nearly half of patients not cured by current multimodal therapies.
- Novel therapeutic strategies are crucial to improve osteosarcoma patient outcomes.
- Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) selectively induces apoptosis in cancer cells, sparing normal cells.
Purpose of the Study:
- To investigate the synergistic effects of TRAIL and Interferon-gamma (IFN-γ) on human osteosarcoma cell lines.
- To determine if IFN-γ can sensitize TRAIL-resistant osteosarcoma cells.
- To elucidate the role of caspases in TRAIL/IFN-γ-induced apoptosis in osteosarcoma.
Main Methods:
- Treatment of four human osteosarcoma cell lines (Saos-2, U2OS, KPDXM, OHS) and one normal human fibroblast cell line (MRC-5) with TRAIL and IFN-γ.
- Assessment of cell viability and apoptosis induction.
- Analysis of caspase cascade activation (caspase-8, caspase-7, PARP) and inhibition studies using caspase inhibitors (zVADfmk, zIETDfmk).
Main Results:
- IFN-γ sensitized one TRAIL-resistant osteosarcoma cell line to TRAIL-mediated apoptosis.
- IFN-γ enhanced TRAIL-induced cell death in two of three TRAIL-sensitive osteosarcoma cell lines.
- Normal fibroblasts (MRC-5) showed no adverse effects from TRAIL and IFN-γ treatment.
- Apoptosis was mediated by a caspase cascade, partly inhibited by caspase inhibitors, highlighting the role of caspases in the observed cell death.
Conclusions:
- Combined treatment with IFN-γ and TRAIL effectively induces cell death in osteosarcoma cell lines.
- This combination therapy warrants further investigation as a potential future treatment strategy for osteosarcoma.
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