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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
West Asia Organization for Cancer Prevention
2018
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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. |
format | Online Article Text |
id | pubmed-6428525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | West Asia Organization for Cancer Prevention |
record_format | MEDLINE/PubMed |
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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