OBJECTIVE.: Despite advances in
chemotherapy and radical surgery, most advanced stage
ovarian cancer patients die from their disease, highlighting the need for the development of novel treatment strategies. The Notch signaling pathway plays an important role in cellular differentiation, proliferation and apoptosis. We hypothesized that the active form of Notch 1, the Notch 1 intracellular domain (NICD), would be overexpressed in
ovarian cancer cells and that depletion of NICD would lead to growth reduction. METHODS.: Following institutional review board approval, NICD expression was analyzed in human
ovarian cancer specimens as well as the
ovarian cancer cell lines OVCAR3, SKOV3, and CaOV3. In addition, the effects of Notch 1 depletion on
ovarian cancer cell growth were detected by
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) growth assay for 6 days following transfection with
siRNA against Notch 1. RESULTS.: Western blot analysis revealed abundant NICD expression in all 3
ovarian cancer cell lines, as well as in 16 of 21 (76%) human
ovarian cancer samples. Following treatment with Notch 1
siRNA, expression of NICD was greatly reduced in all three cell lines. Furthermore, this depletion of NICD was associated with significant growth inhibition of all three
ovarian cancer cell lines. CONCLUSIONS.: NICD was frequently expressed in
ovarian cancer cell lines and human
ovarian cancer specimens. Importantly, depletion of Notch 1 led to growth inhibition of
ovarian cancer cells. These findings support the hypothesis that Notch 1 plays a role in
ovarian cancer proliferation, encouraging the investigation of this pathway as a therapeutic target.