Effects of a gamma secretase inhibitor on the proliferation and invasiveness of oral squamous cell carcinoma cell lines

Abstract

Objective To determine the effects of a gamma secretase inhibitor on the proliferation mediating cell-cycle regulators and invasive activity mediating matrix metalloproteinase (MMP) 9 expression in oral cancer cell lines. Materials and methods In the oral cancer cell lines SAS, HSC-3, and HSC-4, we investigated the expression of components and substrates of gamma secretase using the reverse transcription-polymerase chain reaction (RT-PCR). The proliferation of HSC-4 cells after treatment with a gamma secretase inhibitor was evaluated using a cell proliferation assay, and expressions of cell-cycle regulators were estimated using RT-PCR. The invasive activity of HSC-4 cells after treatment with the gamma secretase inhibitor was determined using a matrigel invasion assay, and MMP9 expression was measured employing RT-PCR. Results RT-PCR revealed the expression of components and substrates of gamma secretase in oral cancer cell lines SAS and HSC-4. HSC-4 cells treated with the gamma secretase inhibitor showed a reduction in proliferation, as well as a decrease in cyclin D1 and cyclin E expression and an increase of p27 (Kip1) expression. Moreover, a reduction of the invasive capacity and MMP9 expression were observed in these cells. Conclusion These results suggest that the inhibition of gamma secretase reduces cell proliferation mediating the expression of cell-cycle regulators and invasive activity mediating MMP9 expression, and that a gamma secretase inhibitor can be applied as a potential therapeutic agent in oral cancer.