Abstract 1604: ABT-869 enhances radiosensitivity of head and neck squamous cell carcinoma cells.

Abstract Purpose: Novel targeted therapeutic strategies to overcome radio-resistance of cancer cells traditionally treated with radiation may improve patient survival with the added benefit of reduced systemic toxicity. Herein, we tested the feasibility of ABT-869 (Linifanib), a multi-receptor tyrosine kinase inhibitor of members of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) receptor families, on radio-sensitization of head and neck squamous cell carcinoma (HNSCC). Materials and Methods: UMSCC-22A and UMSCC-22B cells were treated with ABT-869 and γ-radiation response was determined. Cell viability, cytotoxicity, apoptosis induction and cell cycle distribution were examined by MTT assay, colony formation assay and flow cytometry. In addition, expression of STAT3 and downstream signaling proteins were assessed using western immunoblotting. Results: Treatment with ABT-869 resulted in cell growth inhibition, induction of apoptosis, G2/M cell cycle arrest, reduced phosphorylation of STAT3, which has been linked to radio-resistance, lower expression of cyclin D1, survivin and increase PARP cleavage. In addition, ABT-869 overcame the radio-resistance of the cell lines and significantly enhanced radiation-induced cytotoxicity (p < 0.05). Conclusions: These data suggest the possibility of combining targeted therapeutic such as ABT-869 with radiation to enhance inhibition of cell growth and apoptosis in HNSCC cells. Thus, it may provide a novel therapeutic strategy and improve efficacy of radiation against HNSCC in the future. Citation Format: Heng-Wei Hsu. ABT-869 enhances radiosensitivity of head and neck squamous cell carcinoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1604. doi:10.1158/1538-7445.AM2013-1604