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Open AccessArticle

Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells

1
Department of Diagnostic, Interventional and Pediatric Radiology, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
2
Department of BioMedical Research, University of Bern, 3008 Bern, Switzerland
3
Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
*
Author to whom correspondence should be addressed.
Present address: Department of Chemistry, Bar-Ilan University, Ramat-Gan 5290002, Israel.
Pharmaceuticals 2020, 13(6), 109; https://doi.org/10.3390/ph13060109
Received: 24 April 2020 / Revised: 20 May 2020 / Accepted: 27 May 2020 / Published: 29 May 2020
(This article belongs to the Section Pharmacology)
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. View Full-Text
Keywords: cisplatin; NSCLC; lung cancer; VRAC; resistance cisplatin; NSCLC; lung cancer; VRAC; resistance
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MDPI and ACS Style

Ruprecht, N.; Hofmann, L.; Hungerbühler, M.N.; Kempf, C.; Heverhagen, J.T.; von Tengg-Kobligk, H. Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells. Pharmaceuticals 2020, 13, 109.

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