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

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 trans...

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Autores principales: Akbarzadeh, Maryam, Majidinia, Maryam, Aval, Sedigheh Fekri, Mahbub, Soltanali, Zarghami, Nosratollah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: West Asia Organization for Cancer Prevention 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428525/
https://www.ncbi.nlm.nih.gov/pubmed/30583672
http://dx.doi.org/10.31557/APJCP.2018.19.12.3473
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author Akbarzadeh, Maryam
Majidinia, Maryam
Aval, Sedigheh Fekri
Mahbub, Soltanali
Zarghami, Nosratollah
author_facet Akbarzadeh, Maryam
Majidinia, Maryam
Aval, Sedigheh Fekri
Mahbub, Soltanali
Zarghami, Nosratollah
author_sort Akbarzadeh, Maryam
collection PubMed
description 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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spelling pubmed-64285252019-04-01 Molecular Targeting of Notch Signaling Pathway by DAPT in Human Ovarian Cancer: Possible Anti Metastatic Effects Akbarzadeh, Maryam Majidinia, Maryam Aval, Sedigheh Fekri Mahbub, Soltanali Zarghami, Nosratollah Asian Pac J Cancer Prev Research Article 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. West Asia Organization for Cancer Prevention 2018 /pmc/articles/PMC6428525/ /pubmed/30583672 http://dx.doi.org/10.31557/APJCP.2018.19.12.3473 Text en Copyright: © Asian Pacific Journal of Cancer Prevention http://creativecommons.org/licenses/BY-SA/4.0 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
spellingShingle Research Article
Akbarzadeh, Maryam
Majidinia, Maryam
Aval, Sedigheh Fekri
Mahbub, Soltanali
Zarghami, Nosratollah
Molecular Targeting of Notch Signaling Pathway by DAPT in Human Ovarian Cancer: Possible Anti Metastatic Effects
title Molecular Targeting of Notch Signaling Pathway by DAPT in Human Ovarian Cancer: Possible Anti Metastatic Effects
title_full Molecular Targeting of Notch Signaling Pathway by DAPT in Human Ovarian Cancer: Possible Anti Metastatic Effects
title_fullStr Molecular Targeting of Notch Signaling Pathway by DAPT in Human Ovarian Cancer: Possible Anti Metastatic Effects
title_full_unstemmed Molecular Targeting of Notch Signaling Pathway by DAPT in Human Ovarian Cancer: Possible Anti Metastatic Effects
title_short Molecular Targeting of Notch Signaling Pathway by DAPT in Human Ovarian Cancer: Possible Anti Metastatic Effects
title_sort molecular targeting of notch signaling pathway by dapt in human ovarian cancer: possible anti metastatic effects
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428525/
https://www.ncbi.nlm.nih.gov/pubmed/30583672
http://dx.doi.org/10.31557/APJCP.2018.19.12.3473
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