Down-regulation of Notch1 by Gamma-secretase Inhibitor Contributes to Growth Inhibition and Apoptosis of Ovarian Cancer Cells A2780

Abstract: Objective To investigate the inhibiting effect of gamma-secretase inhibitor, N-N-(3,5-difluorophenacetyl)-L-alanyl-S-phenylglycine t-butyl ester (DAPT), on Notch1 and its effect on the growth and apoptosis of ovarian cancer cells. Methods Expression of Notch 1 and hes1 in four human ovarian cancer cell lines, A2780, SKOV3, HO-8910 and HO-8910PM, and one ovarian surface cell line IOSE 144 were detected by Western blot and quantitative real-time RT-PCR. The effects of DAPT on ovarian cancer cells were measured by MTT assay, flow cytometry, ELISA and colony formation assay. Results Expression of Notch1 and hes1 were found in IOSE144 and all the four human ovarian cancer cell lines, and they were the highest in ovarian cancer cells A2780 compared with other four ovarian cells. Down-regulation of Notch1 expression by DAPT was able to substantially inhibit the growth, induce G1 cell cycle arrest and the apoptosis of A2780 cells in a dose- and time-dependent manner. In addition, hes1 was found to be down-regulated in a dose- and time-dependent manner by DAPT in A2780. Conclusion DAPT could inhibit the growth and induce the apoptosis of A2780 cells in a dose- and time-dependent manner. DAPT inhibiting Notch1 activity represents a potentially attractive strategy of targeted therapy for ovarian cancer.