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Updated: Apr 7, 2026
Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Histone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy
Claudia Blattmann1,2,3,4, Susanne Oertel5,6, Markus Thiemann7,8
1Department of Pediatric Oncology, Hematology and Immunology, University Children's, Hospital of Heidelberg, Heidelberg, Germany. c.blattmann@klinikum-stuttgart.de.
Background:
Minimal improvements in treatment or survival of patients with osteosarcoma have been achieved during the last three decades. Especially in the case of incomplete tumor resection, prognosis remains poor. Heavy ion radiotherapy (HIT) and modern anticancer drugs like histone deacetylase inhibitors (HDACi) have shown promising effects in osteosarcoma in vitro. In this study, we tested the effect of HIT and the combination of HIT and the HDACi suberoylanilide hydroxamic acid (SAHA) in a xenograft mouse model.
Methods:
Osteosarcoma xenografts were established by subcutaneous injection of KHOS-24OS cells and treated with either vehicle (DMSO), SAHA, HIT or HIT and SAHA. Tumor growth was determined and tumor necrosis, proliferation rate, apoptotic rate as well as vessel density were evaluated.
Results:
Here, we show that the combination of HIT and SAHA induced a significant delay of tumor growth through increased rate of apoptosis, increased expression of p53 and p21(Waf1/Cip1), inhibition of proliferation and angiogenesis compared to tumors treated with HIT only.
Conclusion:
HIT and in particular the combination of HIT and histone deacetylase inhibition is a promising treatment strategy in OS and may be tested in clinical trials.
Insights
Heavy ion radiotherapy combined with histone deacetylase inhibitors significantly delays osteosarcoma tumor growth by increasing apoptosis and inhibiting proliferation. This combination therapy shows promise for treating osteosarcoma.
Area of Science:
- Oncology
- Radiotherapy
- Pharmacology
Background:
- Osteosarcoma treatment has seen minimal progress over 30 years, with poor prognosis after incomplete resection.
- Heavy ion radiotherapy (HIT) and histone deacetylase inhibitors (HDACi) show potential against osteosarcoma in vitro.
Purpose of the Study:
- To evaluate the efficacy of HIT and a combination of HIT with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) in an osteosarcoma xenograft mouse model.
Main Methods:
- Osteosarcoma xenografts were established and treated with vehicle, SAHA, HIT, or HIT + SAHA.
- Tumor growth, necrosis, proliferation, apoptosis, and vessel density were assessed.
Main Results:
- The combination of HIT and SAHA significantly delayed tumor growth compared to HIT alone.
- This combination increased apoptosis and p53/p21 expression while inhibiting proliferation and angiogenesis.
Conclusions:
- HIT combined with histone deacetylase inhibition represents a promising treatment strategy for osteosarcoma.
- This combination warrants further investigation in clinical trials for osteosarcoma patients.
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