Histone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy

Radiation Oncology

Jürgen Debus⁴  Albrecht Stenzinger¹  Peter E. Huber⁴  Wilko Weichert³  Volker Ehemann¹  Andreas E. Kulozik³  Eva Roth⁴  Anne Dittmar⁴  Markus Thiemann⁴  Susanne Oertel⁴  Claudia Blattmann² 

[1] Institute of Pathology, University of Heidelberg, Heidelberg, Germany;Pädiatrie 5, Olgahospital, Kriegsbergstr. 62, Stuttgart, 70174, Germany;National Center for Tumor Diseases (NCT), University of Heidelberg, Heidelberg, Germany;Department of Radiation Oncology, German Cancer Research Center, Heidelberg, Germany

关键词: Mouse model;    Radiosensitization;    Suberoylanilide hydroxamic acid;    Histone deacetylase inhibition;    Carbon ion radiotherapy;    Osteosarcoma;   

Others  :  1228499
DOI  :  10.1186/s13014-015-0455-z

 received in 2015-05-05, accepted in 2015-07-06,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Blattmann et al.

【 图 表 】

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