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Novel Combinatorial Strategy Using Thermal Inkjet Bioprinting, Chemotherapy, and Radiation on Human Breast Cancer Cells; an In-Vitro Cell Viability Assessment

Background: Breast cancer (BC) continues to have the second highest mortality amongst women in the United States after lung cancer. For 2021, the American Cancer Association predicted 281,550 new invasive breast cancer cases besides 49,290 new cases of non-invasive breast cancer and 43,600 deaths fr...

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Autores principales: Campbell, Aleli, Gutierrez, Denisse A., Knight, Colin, Vines, Charlotte M., Heydarian, Rosalinda, Philipovskiy, Alexander, Varela-Ramirez, Armando, Boland, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704911/
https://www.ncbi.nlm.nih.gov/pubmed/34947458
http://dx.doi.org/10.3390/ma14247864
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author Campbell, Aleli
Gutierrez, Denisse A.
Knight, Colin
Vines, Charlotte M.
Heydarian, Rosalinda
Philipovskiy, Alexander
Varela-Ramirez, Armando
Boland, Thomas
author_facet Campbell, Aleli
Gutierrez, Denisse A.
Knight, Colin
Vines, Charlotte M.
Heydarian, Rosalinda
Philipovskiy, Alexander
Varela-Ramirez, Armando
Boland, Thomas
author_sort Campbell, Aleli
collection PubMed
description Background: Breast cancer (BC) continues to have the second highest mortality amongst women in the United States after lung cancer. For 2021, the American Cancer Association predicted 281,550 new invasive breast cancer cases besides 49,290 new cases of non-invasive breast cancer and 43,600 deaths from the metastatic disease. A treatment modality is radiation therapy, which is given for local control as well as palliation of patient symptoms. The initial step of new drug development is in-vitro cell studies, which help describe new drug properties and toxicities. However, these models are not optimal, and better ones have yet to be determined. This study uses bioprinting technology to elucidate the sensitivity of tumor cells to the combination of palbociclib (PD) and letrozole (Let) treatment. We hypothesize that this technology could serve as a model to predict treatment outcomes more efficiently. Methods: The breast cancer cell lines MCF7 and MDA-MB-231 as well as the normal breast epithelial cell line, MCF-10A, were treated with PD-Let with and without radiotherapy (RT), and cell viability was compared in pairwise fashion for thermally inkjet bioprinted (TIB) and manually seeded (MS) cells. Results: In absence of radiation, the TIB MCF7 cells have 2.5 times higher viability than manually seeded (MS) cells when treated with 100 µM palbociclib and 10 µM letrozole, a 36% higher viability when treated with 50 µM palbociclib and 10 µM letrozole, and an 8% higher viability when treated with 10 µM palbociclib and 10 µM letrozole. With 10 Gy of radiation, TIB cells had a 45% higher survival rate than MS cells at the lowest palbociclib concentration and a 29% higher survival rate at the intermediate palbociclib concentration. Without radiation treatment, at a concentration of 10 μM PD-Let, TIB MDA-MB-231 cells show a 8% higher viability than MS cells when treated with 10 µM PD and 10 µM Let; at higher drug concentrations, the differences disappeared, but some 1.7% of the TIB MDA-MB-231 cells survived exposure to 150 μM of PD + 10 μM letrozole vs. none of the MS cells. These cells are more radiation sensitive than the other cell lines tested and less sensitive to the combo drug treatments. We observed an 18% higher survival of TIB MCF-10A cells without radiation treatment when exposed to 10 μM PD + 10 μM Let but no difference in cell survival between the two groups when radiation was applied. Independent of growth conditions, TIB cells did not show more resistance to radiation treatment than MS cells, but a higher resistance to the combo treatment was observed, which was most pronounced in the MCF-7 cell line. Conclusion: Based on these results, we suggest that TIB used in in-vitro models could be a feasible strategy to develop and/or test new anticancer drugs.
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spelling pubmed-87049112021-12-25 Novel Combinatorial Strategy Using Thermal Inkjet Bioprinting, Chemotherapy, and Radiation on Human Breast Cancer Cells; an In-Vitro Cell Viability Assessment Campbell, Aleli Gutierrez, Denisse A. Knight, Colin Vines, Charlotte M. Heydarian, Rosalinda Philipovskiy, Alexander Varela-Ramirez, Armando Boland, Thomas Materials (Basel) Article Background: Breast cancer (BC) continues to have the second highest mortality amongst women in the United States after lung cancer. For 2021, the American Cancer Association predicted 281,550 new invasive breast cancer cases besides 49,290 new cases of non-invasive breast cancer and 43,600 deaths from the metastatic disease. A treatment modality is radiation therapy, which is given for local control as well as palliation of patient symptoms. The initial step of new drug development is in-vitro cell studies, which help describe new drug properties and toxicities. However, these models are not optimal, and better ones have yet to be determined. This study uses bioprinting technology to elucidate the sensitivity of tumor cells to the combination of palbociclib (PD) and letrozole (Let) treatment. We hypothesize that this technology could serve as a model to predict treatment outcomes more efficiently. Methods: The breast cancer cell lines MCF7 and MDA-MB-231 as well as the normal breast epithelial cell line, MCF-10A, were treated with PD-Let with and without radiotherapy (RT), and cell viability was compared in pairwise fashion for thermally inkjet bioprinted (TIB) and manually seeded (MS) cells. Results: In absence of radiation, the TIB MCF7 cells have 2.5 times higher viability than manually seeded (MS) cells when treated with 100 µM palbociclib and 10 µM letrozole, a 36% higher viability when treated with 50 µM palbociclib and 10 µM letrozole, and an 8% higher viability when treated with 10 µM palbociclib and 10 µM letrozole. With 10 Gy of radiation, TIB cells had a 45% higher survival rate than MS cells at the lowest palbociclib concentration and a 29% higher survival rate at the intermediate palbociclib concentration. Without radiation treatment, at a concentration of 10 μM PD-Let, TIB MDA-MB-231 cells show a 8% higher viability than MS cells when treated with 10 µM PD and 10 µM Let; at higher drug concentrations, the differences disappeared, but some 1.7% of the TIB MDA-MB-231 cells survived exposure to 150 μM of PD + 10 μM letrozole vs. none of the MS cells. These cells are more radiation sensitive than the other cell lines tested and less sensitive to the combo drug treatments. We observed an 18% higher survival of TIB MCF-10A cells without radiation treatment when exposed to 10 μM PD + 10 μM Let but no difference in cell survival between the two groups when radiation was applied. Independent of growth conditions, TIB cells did not show more resistance to radiation treatment than MS cells, but a higher resistance to the combo treatment was observed, which was most pronounced in the MCF-7 cell line. Conclusion: Based on these results, we suggest that TIB used in in-vitro models could be a feasible strategy to develop and/or test new anticancer drugs. MDPI 2021-12-19 /pmc/articles/PMC8704911/ /pubmed/34947458 http://dx.doi.org/10.3390/ma14247864 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Campbell, Aleli
Gutierrez, Denisse A.
Knight, Colin
Vines, Charlotte M.
Heydarian, Rosalinda
Philipovskiy, Alexander
Varela-Ramirez, Armando
Boland, Thomas
Novel Combinatorial Strategy Using Thermal Inkjet Bioprinting, Chemotherapy, and Radiation on Human Breast Cancer Cells; an In-Vitro Cell Viability Assessment
title Novel Combinatorial Strategy Using Thermal Inkjet Bioprinting, Chemotherapy, and Radiation on Human Breast Cancer Cells; an In-Vitro Cell Viability Assessment
title_full Novel Combinatorial Strategy Using Thermal Inkjet Bioprinting, Chemotherapy, and Radiation on Human Breast Cancer Cells; an In-Vitro Cell Viability Assessment
title_fullStr Novel Combinatorial Strategy Using Thermal Inkjet Bioprinting, Chemotherapy, and Radiation on Human Breast Cancer Cells; an In-Vitro Cell Viability Assessment
title_full_unstemmed Novel Combinatorial Strategy Using Thermal Inkjet Bioprinting, Chemotherapy, and Radiation on Human Breast Cancer Cells; an In-Vitro Cell Viability Assessment
title_short Novel Combinatorial Strategy Using Thermal Inkjet Bioprinting, Chemotherapy, and Radiation on Human Breast Cancer Cells; an In-Vitro Cell Viability Assessment
title_sort novel combinatorial strategy using thermal inkjet bioprinting, chemotherapy, and radiation on human breast cancer cells; an in-vitro cell viability assessment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704911/
https://www.ncbi.nlm.nih.gov/pubmed/34947458
http://dx.doi.org/10.3390/ma14247864
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