Next Article in Journal
Vancomycin-Lipopeptide Conjugates with High Antimicrobial Activity on Vancomycin-Resistant Enterococci
Previous Article in Journal
Physicochemical Investigation of Psoralen Binding to Double Stranded DNA through Electroanalytical and Cheminformatic Approaches

Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells

Department of Diagnostic, Interventional and Pediatric Radiology, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
Department of BioMedical Research, University of Bern, 3008 Bern, Switzerland
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;
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
Show Figures

Graphical abstract

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.

AMA Style

Ruprecht N, Hofmann L, Hungerbühler MN, Kempf C, Heverhagen JT, von Tengg-Kobligk H. Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells. Pharmaceuticals. 2020; 13(6):109.

Chicago/Turabian Style

Ruprecht, Nico, Lukas Hofmann, Martin N. Hungerbühler, Christoph Kempf, Johannes T. Heverhagen, and Hendrik von Tengg-Kobligk. 2020. "Generation of Stable cisPt Resistant Lung Adenocarcinoma Cells" Pharmaceuticals 13, no. 6: 109.

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Back to TopTop