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In Vitro and In Vivo Effects of Docetaxel and Dasatinib in Triple-Negative Breast Cancer: A Research Study
Introduction Triple-negative breast cancer (TNBC) comprises a heterogeneous group of tumors with a single trait in common: an evident aggressive nature with higher rates of relapse and lower overall survival in the metastatic context when compared to other subtypes of breast cancer. To date, not a s...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cureus
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10500968/ https://www.ncbi.nlm.nih.gov/pubmed/37719631 http://dx.doi.org/10.7759/cureus.43534 |
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author | Passos, Ioannis D Papadimitriou, Dimochristos Katsouda, Areti Papavasileiou, Georgios E Galatas, Apostolos Tzitzis, Panagiotis Mpakosi, Alexandra Mironidou- Tzouveleki, Maria |
author_facet | Passos, Ioannis D Papadimitriou, Dimochristos Katsouda, Areti Papavasileiou, Georgios E Galatas, Apostolos Tzitzis, Panagiotis Mpakosi, Alexandra Mironidou- Tzouveleki, Maria |
author_sort | Passos, Ioannis D |
collection | PubMed |
description | Introduction Triple-negative breast cancer (TNBC) comprises a heterogeneous group of tumors with a single trait in common: an evident aggressive nature with higher rates of relapse and lower overall survival in the metastatic context when compared to other subtypes of breast cancer. To date, not a single targeted therapy has been approved for the treatment of TNBC, and cytotoxic chemotherapy remains the standard treatment. In the present experimental study, we examine the effects of the chemotherapeutic docetaxel and the bcr/abl kinase inhibitor dasatinib on TNBC cell lines (in vitro) and on TNBC tumor xenograft mouse models (in vivo). Materials and methods TNBC cell lines were cultivated and treated with various concentrations of docetaxel and dasatinib (5 nM to 100 nM). Cell death and apoptosis were studied by flow cytometry. TNBC cell lines were then injected in BALB/c athymic nude mice to express the tumor in vivo. Four groups of mice were created (group A: control; group B: DOC; group C: DAS; group D: DOC + DAS) and treated, respectively, with the drugs and their combination. Tumors were obtained, maintained in a 10% formaldehyde solution, embedded in paraffin, and sent for further histological evaluation (hematoxylin-eosin staining and immune-histochemical analysis) to assess the tumor growth inhibition. Results The cytotoxic effects of docetaxel seem statistically important, with little effect on apoptosis. The effect of dasatinib in vitro and vivo is statistically important, in terms of apoptosis and tumor reduction, with little adverse effects. Conclusions TNBC is a difficult-to-treat oncologic condition, even in an experimental setting. Promising results concerning the addition of targeted therapies (dasatinib) to the conventional cytotoxic ones (docetaxel) have been shown, awaiting further evaluation. |
format | Online Article Text |
id | pubmed-10500968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cureus |
record_format | MEDLINE/PubMed |
spelling | pubmed-105009682023-09-15 In Vitro and In Vivo Effects of Docetaxel and Dasatinib in Triple-Negative Breast Cancer: A Research Study Passos, Ioannis D Papadimitriou, Dimochristos Katsouda, Areti Papavasileiou, Georgios E Galatas, Apostolos Tzitzis, Panagiotis Mpakosi, Alexandra Mironidou- Tzouveleki, Maria Cureus Pathology Introduction Triple-negative breast cancer (TNBC) comprises a heterogeneous group of tumors with a single trait in common: an evident aggressive nature with higher rates of relapse and lower overall survival in the metastatic context when compared to other subtypes of breast cancer. To date, not a single targeted therapy has been approved for the treatment of TNBC, and cytotoxic chemotherapy remains the standard treatment. In the present experimental study, we examine the effects of the chemotherapeutic docetaxel and the bcr/abl kinase inhibitor dasatinib on TNBC cell lines (in vitro) and on TNBC tumor xenograft mouse models (in vivo). Materials and methods TNBC cell lines were cultivated and treated with various concentrations of docetaxel and dasatinib (5 nM to 100 nM). Cell death and apoptosis were studied by flow cytometry. TNBC cell lines were then injected in BALB/c athymic nude mice to express the tumor in vivo. Four groups of mice were created (group A: control; group B: DOC; group C: DAS; group D: DOC + DAS) and treated, respectively, with the drugs and their combination. Tumors were obtained, maintained in a 10% formaldehyde solution, embedded in paraffin, and sent for further histological evaluation (hematoxylin-eosin staining and immune-histochemical analysis) to assess the tumor growth inhibition. Results The cytotoxic effects of docetaxel seem statistically important, with little effect on apoptosis. The effect of dasatinib in vitro and vivo is statistically important, in terms of apoptosis and tumor reduction, with little adverse effects. Conclusions TNBC is a difficult-to-treat oncologic condition, even in an experimental setting. Promising results concerning the addition of targeted therapies (dasatinib) to the conventional cytotoxic ones (docetaxel) have been shown, awaiting further evaluation. Cureus 2023-08-15 /pmc/articles/PMC10500968/ /pubmed/37719631 http://dx.doi.org/10.7759/cureus.43534 Text en Copyright © 2023, Passos et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Pathology Passos, Ioannis D Papadimitriou, Dimochristos Katsouda, Areti Papavasileiou, Georgios E Galatas, Apostolos Tzitzis, Panagiotis Mpakosi, Alexandra Mironidou- Tzouveleki, Maria In Vitro and In Vivo Effects of Docetaxel and Dasatinib in Triple-Negative Breast Cancer: A Research Study |
title | In Vitro and In Vivo Effects of Docetaxel and Dasatinib in Triple-Negative Breast Cancer: A Research Study |
title_full | In Vitro and In Vivo Effects of Docetaxel and Dasatinib in Triple-Negative Breast Cancer: A Research Study |
title_fullStr | In Vitro and In Vivo Effects of Docetaxel and Dasatinib in Triple-Negative Breast Cancer: A Research Study |
title_full_unstemmed | In Vitro and In Vivo Effects of Docetaxel and Dasatinib in Triple-Negative Breast Cancer: A Research Study |
title_short | In Vitro and In Vivo Effects of Docetaxel and Dasatinib in Triple-Negative Breast Cancer: A Research Study |
title_sort | in vitro and in vivo effects of docetaxel and dasatinib in triple-negative breast cancer: a research study |
topic | Pathology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10500968/ https://www.ncbi.nlm.nih.gov/pubmed/37719631 http://dx.doi.org/10.7759/cureus.43534 |
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