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Histone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy

Blattmann, Claudia ; Oertel, Susanne ; Thiemann, Markus ; Dittmar, Anne ; Roth, Eva ; Kulozik, Andreas E. ; Ehemann, Volker ; Weichert, Wilko ; Huber, Peter E. ; Stenzinger, Albrecht ; Debus, Jürgen

In: Radiation Oncology, 10 (2015), Nr. 146. pp. 1-11. ISSN 1748-717X

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Download (1MB) | Lizenz: Creative Commons LizenzvertragHistone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy by Blattmann, Claudia ; Oertel, Susanne ; Thiemann, Markus ; Dittmar, Anne ; Roth, Eva ; Kulozik, Andreas E. ; Ehemann, Volker ; Weichert, Wilko ; Huber, Peter E. ; Stenzinger, Albrecht ; Debus, Jürgen underlies the terms of Creative Commons Attribution 3.0 Germany

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Abstract

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 p21Waf1/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.

Item Type: Article
Journal or Publication Title: Radiation Oncology
Volume: 10
Number: 146
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 22 Dec 2015 10:32
Date: 2015
ISSN: 1748-717X
Page Range: pp. 1-11
Faculties / Institutes: Medizinische Fakultät Heidelberg > Universitätskinderklinik
Medizinische Fakultät Heidelberg > Radiologische Universitätsklinik
Medizinische Fakultät Heidelberg > Pathologisches Institut
Subjects: 610 Medical sciences Medicine
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