Antiproliferative effects of γ-secretase inhibitor, a Notch signalling inhibitor, in multiple myeloma cells and its molecular mechanism of action

Objectives To investigate the effects of γ-secretase inhibitor (GSI), a Notch signalling inhibitor, on the proliferation of multiple myeloma cells in vitro and its molecular mechanism of action. Methods RPMI 8226 cells were treated with increasing concentrations of GSI (0–20 µmol/l) for 24–72 h. Proliferation was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Cell-cycle analysis was performed on RPMI 8226 cells treated with 0–10 µmol/l GSI for 48 h using flow cytometry. Expression of Notch signalling proteins (Notch1, Jagged 1 and Jagged 2), Bcl-2 and phosphorylated Akt (p-Akt) was determined using Western blotting in RPMI 8226 cells treated with various concentrations of GSI for various time periods. Results GSI inhibited proliferation of RPMI 8226 cells in a concentration- and time-dependent manner by inducing G0/G1 cell-cycle arrest. GSI-mediated antiproliferative effects were associated with significant reductions in the expression of Notch1, Jagged1, Jagged2, p-Akt and Bcl-2. Conclusion Inhibition of the Notch signalling pathway by GSI may be a promising therapeutic approach for the treatment of multiple myeloma.