Radiosensitization by histone deacetylase inhibition in an osteosarcoma mouse model

摘要: Osteosarcomas (OS) are highly malignant and radioresistant tumors. Histone deacetylase inhibitors (HDACi) constitute a novel class of anticancer agents. We sought to investigate the effect combined treatment with suberoylanilide hydroxamic acid (SAHA) radiotherapy in OS vivo. Clonogenic survival human cell lines as well tumor growth delay xenografts were tested after either vehicle, (XRT), SAHA, or XRT SAHA. Tumor proliferation, necrosis, microvascular density, apoptosis, p53/p21 monitored by immunohistochemistry. The CD95 pathway was performed flow cytometry, caspase (3/7/8) activity measurements, functional inhibition death signaling. Combined SAHA markedly reduced surviving fraction cells compared alone. Likewise, dual therapy significantly inhibited vivo alone, reflected impaired angiogenesis, increased apoptosis. Addition HDACi led elevated p53, p21, CD95, CD95L expression. Inhibition signaling HDACi- XRT-induced Our data show that increases radiosensitivity osteosarcoma at least part via ligand-induced thus emerge potentially useful components OS.