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Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells

Platinum compounds represent the backbone of combined chemotherapy protocols for advanced lung cancer. The mechanisms responsible for its frequent primary or acquired resistance to cisplatin (cisPt)-based chemotherapy remains enigmatic. The availability of two cell lines of the same origin, one resi...

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Autores principales: Ruprecht, Nico, Hofmann, Lukas, Hungerbühler, Martin Nils, Kempf, Christoph, Heverhagen, Johannes Thomas, von Tengg-Kobligk, Hendrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345436/
https://www.ncbi.nlm.nih.gov/pubmed/32485798
http://dx.doi.org/10.3390/ph13060109
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author Ruprecht, Nico
Hofmann, Lukas
Hungerbühler, Martin Nils
Kempf, Christoph
Heverhagen, Johannes Thomas
von Tengg-Kobligk, Hendrik
author_facet Ruprecht, Nico
Hofmann, Lukas
Hungerbühler, Martin Nils
Kempf, Christoph
Heverhagen, Johannes Thomas
von Tengg-Kobligk, Hendrik
author_sort Ruprecht, Nico
collection PubMed
description Platinum compounds represent the backbone of combined chemotherapy protocols for advanced lung cancer. The mechanisms responsible for its frequent primary or acquired resistance to cisplatin (cisPt)-based chemotherapy remains enigmatic. The availability of two cell lines of the same origin, one resistant and the other sensitive, will facilitate research to reveal the mechanism of resistance formation. Lung adenocarcinoma cells, A240286S (A24), were cultivated in increasing cisPt concentrations over a prolonged time. After a significant increase in IC(50) was measured, cultivation of the cells was continued in absence of cisPt and IC(50)s determined over a long period (>7 months). As a result, a cell line with lasting, high-level cisPt resistance, designated (D-)A24cisPt8.0, was obtained. The cells were cross-resistant to oxaliplatin and to pemetrexed at a low level. Previous publications have claimed that Leucine-rich repeat-containing protein 8 (LRRC8A and LRRC8D) of the volume-regulated anion channels (VRACs) affect cellular resistance to cisPt. Even though cisPt decreased LRRC8D expression levels, we showed by knockdown and overexpression experiments with LRRC8A and D that these proteins do not govern the observed cisPt resistance. The tumor cell sublines described here provide a powerful model to study the mechanisms of resistance to cisPt in lung cancer cells and beyond.
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spelling pubmed-73454362020-07-09 Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells Ruprecht, Nico Hofmann, Lukas Hungerbühler, Martin Nils Kempf, Christoph Heverhagen, Johannes Thomas von Tengg-Kobligk, Hendrik Pharmaceuticals (Basel) Article Platinum compounds represent the backbone of combined chemotherapy protocols for advanced lung cancer. The mechanisms responsible for its frequent primary or acquired resistance to cisplatin (cisPt)-based chemotherapy remains enigmatic. The availability of two cell lines of the same origin, one resistant and the other sensitive, will facilitate research to reveal the mechanism of resistance formation. Lung adenocarcinoma cells, A240286S (A24), were cultivated in increasing cisPt concentrations over a prolonged time. After a significant increase in IC(50) was measured, cultivation of the cells was continued in absence of cisPt and IC(50)s determined over a long period (>7 months). As a result, a cell line with lasting, high-level cisPt resistance, designated (D-)A24cisPt8.0, was obtained. The cells were cross-resistant to oxaliplatin and to pemetrexed at a low level. Previous publications have claimed that Leucine-rich repeat-containing protein 8 (LRRC8A and LRRC8D) of the volume-regulated anion channels (VRACs) affect cellular resistance to cisPt. Even though cisPt decreased LRRC8D expression levels, we showed by knockdown and overexpression experiments with LRRC8A and D that these proteins do not govern the observed cisPt resistance. The tumor cell sublines described here provide a powerful model to study the mechanisms of resistance to cisPt in lung cancer cells and beyond. MDPI 2020-05-29 /pmc/articles/PMC7345436/ /pubmed/32485798 http://dx.doi.org/10.3390/ph13060109 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ruprecht, Nico
Hofmann, Lukas
Hungerbühler, Martin Nils
Kempf, Christoph
Heverhagen, Johannes Thomas
von Tengg-Kobligk, Hendrik
Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells
title Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells
title_full Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells
title_fullStr Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells
title_full_unstemmed Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells
title_short Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells
title_sort generation of stable cispt resistant lung adenocarcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345436/
https://www.ncbi.nlm.nih.gov/pubmed/32485798
http://dx.doi.org/10.3390/ph13060109
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