Molecular Targeting of Notch Signaling Pathway by DAPT in Human Ovarian Cancer: Possible Anti Metastatic Effects

Abstract

Background: Ovarian cancer is one of the most important gynecological malignancies, causing significant mortality.<br />Recently, there has been extensive attention to the involvement of signaling cascades in its initiation/progression. In this<br />study, we focused on the possible role of Notch signal transduction in proliferation and metalloproteinase 2 and 9 function<br />in human ovarian cancer OVCAR-3 cells. Methods: MTT proliferation assays were used to evaluate effects of a DAPT<br />inhibitor on cell proliferation. For measurement of Hes-1 mRNA levels, quantitative reverse transcription polymerase<br />chain reaction (qRT-PCR) was applied following 48 h incubation with the inhibitor. In addition, metalloproteinase<br />(MMPs) activity was assessed by zymography. Results: Inhibition of Notch signaling resulted in a significant reduction<br />in OVCAR-3 cell proliferation. Additionally, DAPT treatment of cells significantly decreased Hes-1 mRNA levels<br />(p < 0.05) as well as activity of MMP-2 and -9 (p < 0.05). Conclusion: Our results suggested that suppression of Notch<br />signaling by a specific inhibitor can effectively decrease proliferation and the potential for metastasis of OVCAR-3 cells<br />via a reduction in the activity of metalloproteinases 2 and 9. Thus, pharmacological targeting of the Notch signaling<br />pathway could be a promising future treatment for ovarian cancer.