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Updated: Apr 18, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
CYC1 silencing sensitizes osteosarcoma cells to TRAIL-induced apoptosis
Guodong Li1, Dong Fu, Wenqing Liang
1Department of Orthopedics, Tenth People's Hospital of Tongji University, Shanghai, China.
Aims:
Osteosarcoma (OS) is an aggressive bone malignancy with poor prognosis. Many OS cells are resistant to apoptotic induction by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). In our previous study, we found that the serum level of cytochrome c1 (CYC1) is significantly higher in OS patients than in healthy subjects. Our aim was to investigate the effects of CYC1 silencing on TRAIL-induced apoptosis in human OS in vitro and in vivo along with the underlying mechanisms.
Methods:
First, we determined the expression of CYC1 in human OS tumors and cell lines versus normal adjacent tissues and cell line. We then studied the effects of CYC1 silencing alone or in combination with TRAIL on OS cell growth and apoptosis in vitro and OS tumorigenesis in vivo.
Results:
We found that CYC1 is overexpressed in human OS tissues and cell lines. CYC1 silencing by shRNA transfection inhibits proliferation, slightly induces apoptosis in human OS cells in vitro, and suppresses human OS tumor growth in a mouse xenograft model in vivo. Additionally, CYC1 silencing sensitizes OS to TRAIL-induced apoptosis in vitro and in vivo. Our results also showed that CYC1 silencing significantly reduces complex III activity and potentiates TRAIL-induced cytochrome c release and caspase-9 activation in OS cells, suggesting that CYC1 silencing acts via the mitochondria-dependent apoptotic pathway.
Conclusion:
Taken together, our results provide evidence that CYC1 plays an important role in OS tumorigenesis, and modulation of CYC1 may be an effective strategy to potentiate OS to apoptotic induction by TRAIL.
Insights
Silencing cytochrome c1 (CYC1) inhibits osteosarcoma (OS) growth and sensitizes it to TRAIL-induced apoptosis. This suggests targeting CYC1 could enhance cancer treatment efficacy for OS patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma (OS) is an aggressive bone cancer with limited treatment options.
- Many OS cells exhibit resistance to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
- Elevated serum levels of cytochrome c1 (CYC1) have been observed in OS patients.
Purpose of the Study:
- To investigate the impact of CYC1 silencing on TRAIL-induced apoptosis in human OS.
- To explore the underlying molecular mechanisms of CYC1's role in OS.
- To evaluate CYC1 silencing as a potential therapeutic strategy for OS.
Main Methods:
- Determined CYC1 expression in OS tissues and cell lines.
- Utilized shRNA to silence CYC1 in OS cells and assessed effects on proliferation and apoptosis in vitro.
- Evaluated the effects of CYC1 silencing combined with TRAIL on OS cell growth and tumor growth in vivo using a mouse xenograft model.
Main Results:
- CYC1 is overexpressed in OS tissues and cell lines.
- CYC1 silencing inhibited OS cell proliferation, induced apoptosis, and suppressed tumor growth in vivo.
- CYC1 silencing sensitized OS cells to TRAIL-induced apoptosis by affecting mitochondrial complex III activity and cytochrome c release.
- The mechanism involves the mitochondria-dependent apoptotic pathway, including caspase-9 activation.
Conclusions:
- CYC1 plays a significant role in osteosarcoma tumorigenesis.
- Modulating CYC1 expression can enhance the sensitivity of OS cells to TRAIL-induced apoptosis.
- Targeting CYC1 represents a promising strategy to improve therapeutic outcomes for osteosarcoma.
