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High cofilin-1 levels correlate with cisplatin resistance in lung adenocarcinomas

  • Research Article
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Tumor Biology

Abstract

High cofilin-1 levels have been shown to be an accurate prognostic biomarker in non-small cell lung cancer (NSCLC) and a predictive factor in drug resistance. Herein we explore the role of cofilin-1 in cis-diamminedichloroplatinum(II) (cisplatin) resistance. We evaluated cofilin-1 levels in intrinsically cisplatin-resistant A549 (ICR-A549) cells and determined the cisplatin toxicity in A549 cells transiently transfected and overexpressing CFL1 plasmid. Moreover, expression levels (activity) of the CFL1 gene network were analyzed in a cisplatin-resistant human lung adenocarcinoma cell panel. ICR-A549 cells, selected by challenging parental cells with 10-fold drug GI50 value, presented a sixfold increase in cisplatin GI50 value and an increased cofilin-1 immunocontent (P < 0.01). In addition, cells transfected with cofilin-1 became more resistant to cisplatin (P < 0.01). High activity of the CFL1 gene network was found in a cisplatin-resistant adenocarcinoma cell panel (P < 0.01). In vitro evidences suggest that cofilin-1 is a biological predictor of cisplatin resistance, supporting new treatment initiatives based on cofilin-1 levels to guide chemotherapeutic interventions in NSCLC patients.

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Acknowledgments

This work was supported by the Brazilian funds MCT/CNPq Universal (470306/2011-4), PRONEX/FAPERGS (1000274), PRONEM/FAPERGS (11/2032-5), PqG/FAPERGS (2414-2551/12-8), and MCT/CNPq INCT-TM (573671/2008-7). F.K. received a fellowship from MCT/CNPq (303613/2008-4).

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Authors and Affiliations

  1. Laboratório de Bioquímica Celular, Departamento de Bioquímica, ICBS/UFRGS, 2600 Ramiro Barcelos St, 90035-003, Porto Alegre, Rio Grande do Sul, Brazil

    Matheus Becker, Marco Antônio De Bastiani, Carolina Beatriz Müller & Fábio Klamt

  2. Instituto Nacional de Ciência e Tecnologia-Translacional em Medicina (INCT-TM), 90035-903, Porto Alegre, Rio Grande do Sul, Brazil

    Matheus Becker, Marco Antônio De Bastiani, Carolina Beatriz Müller, Mauro Antônio A. Castro & Fábio Klamt

  3. Laboratório de Cardiologia Celular e Molecular, IC/FUC, 90620-000, Porto Alegre, Rio Grande do Sul, Brazil

    Melissa M. Markoski

  4. Hospital de Clínicas de Porto Alegre (HCPA)/UFRGS, 90035-903, Porto Alegre, Rio Grande do Sul, Brazil

    Mauro Antônio A. Castro

Authors
  1. Matheus Becker
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  2. Marco Antônio De Bastiani
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  3. Carolina Beatriz Müller
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  4. Melissa M. Markoski
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  5. Mauro Antônio A. Castro
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  6. Fábio Klamt
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Corresponding author

Correspondence to Fábio Klamt.

Additional information

Matheus Becker and Marco Antônio De Bastiani contributed equally to this work.

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Becker, M., De Bastiani, M.A., Müller, C.B. et al. High cofilin-1 levels correlate with cisplatin resistance in lung adenocarcinomas. Tumor Biol. 35, 1233–1238 (2014). https://doi.org/10.1007/s13277-013-1164-6

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  • DOI: https://doi.org/10.1007/s13277-013-1164-6

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