Effect of Mifepristone on Migration and Proliferation of Oral Cancer Cells

Glucocorticoid receptor (GR) over-expression has been linked to increased tumour aggressiveness and treatment resistance. GR antagonists have been shown to enhance treatment effectiveness. Emerging research has investi-10 gated mifepristone, a GR antagonist, as an anti-cancer agent with limited research in the context of oral cancer. This study investigated the effect of mifepristone at micromolar (μM) concentrations of 1, 5, 10 and 20, on proliferation and migration of oral cancer cells, at 24 and 48 hours. Scratch and scatter assays were utilised to assess cell migration, MTT assay to measure cell proliferation, Western blotting to investigate the expression of GR and the activation of underlying Phosphoinositide 3- kinase (PI3K-)/protein kinase B (Akt) and mitogen activated protein kinase (MAPK) signalling pathways, and immunofluorescence (IF) to determine the localisation of proteins in HaCaT (Immortalised human skin keratinocytes), TYS (Human adenosquamous cell carcinoma), and SAS-H1 cells (Squamous cell carcinoma of the floor of the mouth). Mifepristone resulted in a dose-dependent reduction in proliferation of HaCaT, TYS, and SAS-H1 cells. 20 μM mifepristone effectively reduced collective migration and scattering of oral cancer cells, consistent with the suppression of the PI3K-Akt and MAPK signalling pathways, and reduced expression of N-Cadherin. An elongated cell morphology was however observed, which may be linked to the localisation pattern of E-Cadherin in response to mifepristone. Overall, this study found that a high concentration of mifepristone was effective in suppression of migration and proliferation of oral cancer cells via the inhibition of PI3K-Akt and MAPK signalling pathways. Further investigation is needed to define its impact on epithelial mesenchymal transition (EMT) markers.