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

ObjectiveTo 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 methodsIn 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.ResultsRT-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.ConclusionThese 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.