Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids

Abstract One of the hallmarks of cancers is their ability to develop resistance against therapeutic agents. Therefore, developing effective in vitro strategies to identify drug resistance remains of paramount importance for successful treatment. One of the ways cancer cells achieve drug resistance i...

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Autores principales:	Mohammad Azharuddin, Karin Roberg, Ashis Kumar Dhara, Mayur Vilas Jain, Padraig Darcy, Jorma Hinkula, Nigel K. H. Slater, Hirak K. Patra
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/911f8b141a544fcaad0f82480ee827e5
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spelling	oai:doaj.org-article:911f8b141a544fcaad0f82480ee827e52021-12-02T13:35:11ZDissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids10.1038/s41598-019-56273-62045-2322https://doaj.org/article/911f8b141a544fcaad0f82480ee827e52019-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-56273-6https://doaj.org/toc/2045-2322Abstract One of the hallmarks of cancers is their ability to develop resistance against therapeutic agents. Therefore, developing effective in vitro strategies to identify drug resistance remains of paramount importance for successful treatment. One of the ways cancer cells achieve drug resistance is through the expression of efflux pumps that actively pump drugs out of the cells. To date, several studies have investigated the potential of using 3-dimensional (3D) multicellular tumor spheroids (MCSs) to assess drug resistance; however, a unified system that uses MCSs to differentiate between multi drug resistance (MDR) and non-MDR cells does not yet exist. In the present report we describe MCSs obtained from post-diagnosed, pre-treated patient-derived (PTPD) cell lines from head and neck squamous cancer cells (HNSCC) that often develop resistance to therapy. We employed an integrated approach combining response to clinical drugs and screening cytotoxicity, monitoring real-time drug uptake, and assessing transporter activity using flow cytometry in the presence and absence of their respective specific inhibitors. The report shows a comparative response to MDR, drug efflux capability and reactive oxygen species (ROS) activity to assess the resistance profile of PTPD MCSs and two-dimensional (2D) monolayer cultures of the same set of cell lines. We show that MCSs provide a robust and reliable in vitro model to evaluate clinical relevance. Our proposed strategy can also be clinically applicable for profiling drug resistance in cancers with unknown resistance profiles, which consequently can indicate benefit from downstream therapy.Mohammad AzharuddinKarin RobergAshis Kumar DharaMayur Vilas JainPadraig DarcyJorma HinkulaNigel K. H. SlaterHirak K. PatraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohammad Azharuddin Karin Roberg Ashis Kumar Dhara Mayur Vilas Jain Padraig Darcy Jorma Hinkula Nigel K. H. Slater Hirak K. Patra Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids
description	Abstract One of the hallmarks of cancers is their ability to develop resistance against therapeutic agents. Therefore, developing effective in vitro strategies to identify drug resistance remains of paramount importance for successful treatment. One of the ways cancer cells achieve drug resistance is through the expression of efflux pumps that actively pump drugs out of the cells. To date, several studies have investigated the potential of using 3-dimensional (3D) multicellular tumor spheroids (MCSs) to assess drug resistance; however, a unified system that uses MCSs to differentiate between multi drug resistance (MDR) and non-MDR cells does not yet exist. In the present report we describe MCSs obtained from post-diagnosed, pre-treated patient-derived (PTPD) cell lines from head and neck squamous cancer cells (HNSCC) that often develop resistance to therapy. We employed an integrated approach combining response to clinical drugs and screening cytotoxicity, monitoring real-time drug uptake, and assessing transporter activity using flow cytometry in the presence and absence of their respective specific inhibitors. The report shows a comparative response to MDR, drug efflux capability and reactive oxygen species (ROS) activity to assess the resistance profile of PTPD MCSs and two-dimensional (2D) monolayer cultures of the same set of cell lines. We show that MCSs provide a robust and reliable in vitro model to evaluate clinical relevance. Our proposed strategy can also be clinically applicable for profiling drug resistance in cancers with unknown resistance profiles, which consequently can indicate benefit from downstream therapy.
format	article
author	Mohammad Azharuddin Karin Roberg Ashis Kumar Dhara Mayur Vilas Jain Padraig Darcy Jorma Hinkula Nigel K. H. Slater Hirak K. Patra
author_facet	Mohammad Azharuddin Karin Roberg Ashis Kumar Dhara Mayur Vilas Jain Padraig Darcy Jorma Hinkula Nigel K. H. Slater Hirak K. Patra
author_sort	Mohammad Azharuddin
title	Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids
title_short	Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids
title_full	Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids
title_fullStr	Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids
title_full_unstemmed	Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids
title_sort	dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/911f8b141a544fcaad0f82480ee827e5
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Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids

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