Sensitizing oral squamous cell carcinoma to chemotherapy by targeted disruption of cancer stem cells using an NFκB inhibitor

Abstract

Introduction

Oral squamous cell carcinoma (OSCC) shows a limited response to current systemic treatments, and this resistance could be associated with cancer stem cells (CSC). NFκB is an activated pathway in several malignancies, including head and neck cancer. Here we evaluated the role of NFκB inhibitor on the behavior of CSC derived from OSCC.

Material and methods

Emetine was used as an NFκB inhibitor. CSC presence was assessed by tumorspheres, and the emetine IC₅₀ was determined in this specific cell population. Also, the CSC was quantified by the enzymatic activity of aldehyde dehydrogenases (ALDH) using flow cytometry. Immunofluorescence staining for phosphorylated protein p65 was used to identify the NFκB levels of tumor cells. Finally, OSCC cells were sensitized with emetine for 24 hours followed by administration of cisplatin (IC₅₀).

Results

The IC₅₀ of emetine in CSC OSCC was 0.5μM. We then treated the OSCC cells with the emetine IC₅₀, which showed a significant reduction of the ALDH population, while the NFκB pathway was inhibited. Further, emetine sensitized OSCC cells to cisplatin, resulting in a reduction of the IC₅₀ from 3.9μM to 1.3μM for SCC9.

Conclusion

Our results suggested that CSCs play an important role in tumor resistance to chemotherapy and highlight the disruption of these cells by the NFκB inhibition as a promisor target therapy.