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

Document Type : Research Articles

Authors

1 Department of Biochemistry, Higher Education Institute of Rab-Rashid, Tabriz, Iran.

2 Solid Tumor Research Center, Urmia University of Medical Science, Urmia, Iran.

3 Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

4 Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract

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

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Volume 19, Issue 12
December 2018
Pages 3473-3477
  • Receive Date: 15 February 2018
  • Revise Date: 08 September 2018
  • Accept Date: 04 November 2018
  • First Publish Date: 01 December 2018