Interferon-α Promotes the Expression of Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma

Objectives: IFN alpha can stimulate an antitumor immune response and has a direct inhibition on cancer cells. This study is to test whether IFNa can activate dormant cancer stem cell (CSC) in oral squamous cell carcinoma (OSCC) to facilitate their elimination by chemotherapy. Materials and methods: Nude mouse transplantation tumor model was established and administrated with IFNa and saline. The influence on CD44 and ALDH1A1 expression under IFNa treatment was detected by in vivo experiments. Flow cytometry, western blot, and immunofluorescence were used to detect the expression of CD44 and ALDH1A1 after INFa treatment in OSCC cell lines. Tumorsphere formation assay was conducted under incubation with IFNa for 2 weeks. Chromatin immunoprecipitation (ChIP) assays was used to examine the IFNa-induced transcriptional regulation of CD44 and ALDH1A1 expression. That IFN alpha-primed enhanced killing effect of chemotherapy was evaluated by MTT and western blot. Results: IFNa transcriptionally activated the expression of CD44 and ALDH1A1 expression both in vivo and in vitro. IFN alpha-primed enhanced the cytotoxic inhibition effect of CDDP, erlotinib and nimotuzumab on OSCC cells. Conclusion: These results suggest that IFNa could be administrated to patients prior to chemotherapeutic drugs, which will facilitate the killing of cancer stem cells in OSCC.