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Pharmacological approaches in an experimental model of non-small cell lung cancer: Effects on tumor biology.

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dc.contributor.author Mateu Jiménez, Mercè, 1990-
dc.contributor.author Fermoselle Pérez, Clara, 1985-
dc.contributor.author Rojo, Federico
dc.contributor.author Mateu de Antonio, Francisco Javier
dc.contributor.author Peña, Raúl
dc.contributor.author Urtreger, Alejandro J.
dc.contributor.author Diament, Miriam J.
dc.contributor.author Joffé, Elisa D. Bal de Kier
dc.contributor.author Pijuan Andujar, Lara
dc.contributor.author García de Herreros, Antonio
dc.contributor.author Barreiro Portela, Esther
dc.date.accessioned 2017-01-25T11:20:18Z
dc.date.issued 2016
dc.identifier.citation Mateu-Jimenez M, Fermoselle C, Rojo F, Mateu J, Peña R, Urtreger AJ. et al. Pharmacological approaches in an experimental model of non-small cell lung cancer: effects on tumor biology. Curr Pharm Des. 2016;22(34):5300-10. DOI: 10.2174/1381612822666160623065523
dc.identifier.issn 1381-6128
dc.identifier.uri http://hdl.handle.net/10230/27984
dc.description.abstract Lung cancer (LC) remains the leading cause of cancer mortality worldwide, and non-small cell LC (NSCLC) represents 80% of all LC. Oxidative stress and inflammation, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-κB, and mitogen activated protein kinases (MAPK) participate in LC pathophysiology. Currently available treatment for LC is limited and in vivo models are lacking. We hypothesized that antioxidants and NF- κB, MAPK, and proteasome inhibitors may exert an antitumoral response through attenuation of several key biological mechanisms that promote tumorigenesis and cancer cell growth. Body and tumor weights, oxidative stress, antioxidants, inflammation, NF-κB p65 expression, fibulins, apoptosis, autophagy, tumor and stroma histology were evaluated in the subcutaneous tumor of LC (LP07 adenocarcinoma) BALB/c mice, with and without concomitant treatment with NF-κB (sulfasalazine), MEK (U0126), and proteasome (bortezomib) inhibitors, and N-acetyl cysteine (NAC). Compared to LC control mice, in subcutanous tumors, the four pharmacological agents reduced oxidative stress markers and tumor proliferation (ki-67). Inflammation and NF-κB p65 expression were attenuated by NF-κB and MAPK inhibitors, and the latter also enhanced apoptotic markers. Catalase was induced by the three inhibitors, while bortezomib also promoted superoxide dismutase expression. NF-κB and MEK inhibitors significantly reduced tumor burden through several biological mechanisms that favored tumor degradation and attenuated tumor proliferation. These two pharmacological agents may enhance the anti-tumor activity of selectively targeted therapeutic strategies for LC. Proteasomal inhibition using bortezomib rather promotes tumor degradation, while treatment with antioxidants cannot be recommended. This experimental model supports the use of adjuvant drugs for the improvement of LC treatment.
dc.description.sponsorship This study has been supported by FIS 11/02029 (FEDER); FIS 14/00713 (FEDER); FUCAP 2011; FUCAP 2012; ISCIII/FEDER (RD12/0036/0005) (Spain).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Bentham Science Publishers
dc.relation.ispartof Current Pharmaceutical Design. 2016;22(34):5300-10
dc.rights © Bentham Science Publishers. Article published in Mateu-Jimenez M, Curr Pharm Des. 22(34), 2016. The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/10.2174/1381612822666160623065523
dc.subject.other Pulmons -- Càncer
dc.subject.other Càncer -- Tractament
dc.title Pharmacological approaches in an experimental model of non-small cell lung cancer: Effects on tumor biology.
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.2174/1381612822666160623065523
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion

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