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Drug-Resistant Urothelial Cancer Cell Lines Display Diverse Sensitivity Profiles to Potential Second-Line Therapeutics.

Vallo, Stefan, Michaelis, Martin, Rothweiler, Florian, Bartsch, Georg, Gust, Kilian M, Limbart, Dominik M, Rödel, Franz, Wezel, Felix, Haferkamp, Axel, Cinatl, Jindrich and others. (2015) Drug-Resistant Urothelial Cancer Cell Lines Display Diverse Sensitivity Profiles to Potential Second-Line Therapeutics. Translational oncology, 8 (3). pp. 210-216. ISSN 1936-5233. (doi:10.1016/j.tranon.2015.04.002) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:49032)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL:
http://dx.doi.org/10.1016/j.tranon.2015.04.002

Abstract

Combination chemotherapy with gemcitabine and cisplatin in patients with metastatic urothelial cancer of the bladder frequently results in the development of acquired drug resistance. Availability of cell culture models with acquired resistance could help to identify candidate treatments for an efficient second-line therapy. Six cisplatin- and six gemcitabine-resistant cell lines were established. Cell viability assays were performed to evaluate the sensitivity to 16 different chemotherapeutic substances. The activity of the drug transporter ATP-binding cassette transporter, subfamily B, member 1 (ABCB1, a critical mediator of multidrug resistance in cancer) was evaluated using fluorescent ABCB1 substrates. For functional assessment, cells overexpressing ABCB1 were generated by transduction with a lentiviral vector encoding for ABCB1, while zosuquidar was used for selective inhibition. In this study, 8 of 12 gemcitabine- or cisplatin-resistant cell lines were cross-resistant to carboplatin, 5 to pemetrexed, 4 to methotrexate, 3 to oxaliplatin, 5-fluorouracil, and paclitaxel, and 2 to cabazitaxel, larotaxel, docetaxel, topotecan, doxorubicin, and mitomycin c, and 1 of 12 cell lines was cross-resistant to vinflunine and vinblastine. In one cell line with acquired resistance to gemcitabine (TCC-SUP(r)GEMCI(20)), cross-resistance seemed to be mediated by ABCB1 expression. Our model identified the vinca alkaloids vinblastine and vinflunine, in Europe an already approved second-line therapeutic for metastatic bladder cancer, as the most effective compounds in urothelial cancer cells with acquired resistance to gemcitabine or cisplatin. These results demonstrate that this in vitro model can reproduce clinically relevant results and may be suitable to identify novel substances for the treatment of metastatic bladder cancer.

Item Type: Article
DOI/Identification number: 10.1016/j.tranon.2015.04.002
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Martin Michaelis
Date Deposited: 16 Jun 2015 13:50 UTC
Last Modified: 17 Aug 2022 10:58 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/49032 (The current URI for this page, for reference purposes)

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