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Synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells

BACKGROUND: The prognosis for patients with disseminated lung cancer is poor and current treatments have limited survival benefit as resistance often occurs, and is often associated with significant toxicity. A possible strategy to improve treatment and evade chemoresistance may be to find new combi...

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Autores principales: Sooman, Linda, Gullbo, Joachim, Bergqvist, Michael, Bergström, Stefan, Lennartsson, Johan, Ekman, Simon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667477/
https://www.ncbi.nlm.nih.gov/pubmed/29096687
http://dx.doi.org/10.1186/s13104-017-2842-z
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author Sooman, Linda
Gullbo, Joachim
Bergqvist, Michael
Bergström, Stefan
Lennartsson, Johan
Ekman, Simon
author_facet Sooman, Linda
Gullbo, Joachim
Bergqvist, Michael
Bergström, Stefan
Lennartsson, Johan
Ekman, Simon
author_sort Sooman, Linda
collection PubMed
description BACKGROUND: The prognosis for patients with disseminated lung cancer is poor and current treatments have limited survival benefit as resistance often occurs, and is often associated with significant toxicity. A possible strategy to improve treatment and evade chemoresistance may be to find new combinations of drugs. The aim of this study was to analyze the potential of combining proteasome inhibitors (PIs) with chemotherapeutic drugs used in the routine treatment for lung cancer patients. RESULTS: The median-effect method was applied to the Fluorometric Microculture Cytotoxicity Assay (FMCA) to evaluate effects of combining two different PIs (bortezomib and b-AP15) with clinically used chemotherapeutic drugs representing different mechanisms of action (cisplatin, gefitinib, gemcitabine and vinorelbine) in two lung cancer cell lines (one sensitive and one resistant). Proteasome inhibition in combination with cisplatin, gemcitabine or vinorelbine had synergistic effects in at least one of the tested cell lines. Furthermore, the effect of gefitinib appeared strongly potentiated by the PI in the least resistant lung cancer cell line, although the level of synergy could not be determined with the median-effect method. CONCLUSIONS: Combining PIs with cisplatin, gefitinib, gemcitabine or vinorelbine show potential as new combination chemotherapy for the treatment of lung cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-017-2842-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-56674772017-11-08 Synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells Sooman, Linda Gullbo, Joachim Bergqvist, Michael Bergström, Stefan Lennartsson, Johan Ekman, Simon BMC Res Notes Research Article BACKGROUND: The prognosis for patients with disseminated lung cancer is poor and current treatments have limited survival benefit as resistance often occurs, and is often associated with significant toxicity. A possible strategy to improve treatment and evade chemoresistance may be to find new combinations of drugs. The aim of this study was to analyze the potential of combining proteasome inhibitors (PIs) with chemotherapeutic drugs used in the routine treatment for lung cancer patients. RESULTS: The median-effect method was applied to the Fluorometric Microculture Cytotoxicity Assay (FMCA) to evaluate effects of combining two different PIs (bortezomib and b-AP15) with clinically used chemotherapeutic drugs representing different mechanisms of action (cisplatin, gefitinib, gemcitabine and vinorelbine) in two lung cancer cell lines (one sensitive and one resistant). Proteasome inhibition in combination with cisplatin, gemcitabine or vinorelbine had synergistic effects in at least one of the tested cell lines. Furthermore, the effect of gefitinib appeared strongly potentiated by the PI in the least resistant lung cancer cell line, although the level of synergy could not be determined with the median-effect method. CONCLUSIONS: Combining PIs with cisplatin, gefitinib, gemcitabine or vinorelbine show potential as new combination chemotherapy for the treatment of lung cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-017-2842-z) contains supplementary material, which is available to authorized users. BioMed Central 2017-11-02 /pmc/articles/PMC5667477/ /pubmed/29096687 http://dx.doi.org/10.1186/s13104-017-2842-z Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Sooman, Linda
Gullbo, Joachim
Bergqvist, Michael
Bergström, Stefan
Lennartsson, Johan
Ekman, Simon
Synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells
title Synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells
title_full Synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells
title_fullStr Synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells
title_full_unstemmed Synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells
title_short Synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells
title_sort synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667477/
https://www.ncbi.nlm.nih.gov/pubmed/29096687
http://dx.doi.org/10.1186/s13104-017-2842-z
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