Preferential targeting of cancer stem cells in the radiosensitizing effect of ABT-737 on HNSCC
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Marion Gilormini1,2, Céline Malesys1,2, Emma Armandy1,2, Patrick Manas3, Jean-Baptiste Guy1,2, Nicolas Magné1,2,5, Claire Rodriguez-Lafrasse1,2,4, Dominique Ardail1,2,4
1Université Lyon I, Faculté de Médecine-Lyon-Sud, Oullins, France
2Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Oullins, France
3UMS3444 BioSciences Gerland-Lyon Sud, PBES, Lyon, France
4Hospices-Civils-de-Lyon, CHLS, Pierre-Bénite, France
5Institut de Cancérologie L. Neuwirth, St Etienne, France
Dominique Ardail, e-mail: email@example.com
Keywords: head and neck squamous cell carcinoma, ABT-737, radiation, Bcl-2 family, cancer stem cells
Received: October 16, 2015 Accepted: January 13, 2016 Published: February 26, 2016
Head and neck squamous cell carcinomas (HNSCC) are common human malignancies with poor clinical outcomes. The 5-year survival rates for patients with advanced stage HNSCC have not changed appreciably in the past few decades, underscoring a dire need for improved therapeutic options. HNSCC is frequently characterized by overexpression of anti-apoptotic Bcl-2 family members. Increased levels of these anti-apoptotic proteins have been associated with radio- and chemoresistance and poor clinical outcome. The aim of this study was to evaluate combined effects of radiation and ABT-737, a BH3-mimetic molecule, in HNSCC. Although ABT-737, as a single agent, was largely ineffective at promoting HNSCC cell death, we found that combining ABT-737 and radiation induced strong synergistic apoptosis in HNSCC cell lines and delayed tumoral growth in vivo. Moreover, we demonstrated for the first time that ABT-737, alone or in combination with radiation, can efficiently eliminate cancer stem cells (CSCs). Altogether, our results indicate that therapy targeting anti-apoptotic Bcl-2 family members could be a highly effective potential adjuvant to radiotherapy capable of targeting CSCs in HNSCC and therefore overcoming cancer recurrence and metastasis.
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