Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells

Ruprecht, Nico; Hofmann, Lukas; Hungerbühler, Martin Nils; Kempf, Christoph; Heverhagen, Johannes; von Tengg-Kobligk, Hendrik (2020). Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells. Pharmaceuticals, 13(6), p. 109. MDPI 10.3390/ph13060109

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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 IC50 was measured, cultivation of the cells was continued in absence of cisPt and IC50s 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic, Interventional and Paediatric Radiology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Radiologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Radiologie

UniBE Contributor:

Ruprecht, Nico; Hungerbuehler, Martin; Kempf, Christoph; Heverhagen, Johannes and von Tengg-Kobligk, Hendrik

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1424-8247

Publisher:

MDPI

Language:

English

Submitter:

Christoph Kempf

Date Deposited:

01 Feb 2021 13:50

Last Modified:

01 Feb 2021 13:59

Publisher DOI:

10.3390/ph13060109

PubMed ID:

32485798

BORIS DOI:

10.48350/144445

URI:

https://boris.unibe.ch/id/eprint/144445

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