Journal
ONCOTARGET
Volume 7, Issue 45, Pages 73032-73044Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.12195
Keywords
salivary cancer; irradiation; IKK alpha; cancer stem cells; radio-adaptive
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Funding
- Capes Foundation within Ministry of Education, Brazil [BEX/99999.007990/2014-06]
- University of Michigan School of Dentistry faculty grant
- Cancer Center Support Grant [P30 CA046592]
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Patients with mucoepidermoid carcinoma (MEC) experience low survival rates and high morbidity following treatment, yet the intrinsic resistance of MEC cells to ionizing radiation (IR) and the mechanisms underlying acquired resistance remain unexplored. Herein, we demonstrated that low doses of IR intrinsically activated NF kappa B in resistant MEC cell lines. Moreover, resistance was significantly enhanced in IR-sensitive cell lines when NF kappa B pathway was stimulated. Pharmacological inhibition of the IKK-beta/I kappa B alpha/NF kappa B axis, using a single dose of FDA-approved Emetine, led to a striking sensitization of MEC cells to IR and a reduction in cancer stem cells. We achieved a major step towards better understanding the basic mechanisms involved in IR-adaptive resistance in MEC cell lines and how to efficiently overcome this critical problem.
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