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-ca
- dc.contributor.author Fermoselle Pérez, Clara, 1985-ca
- dc.contributor.author Rojo, Federicoca
- dc.contributor.author Mateu de Antonio, Francisco Javierca
- dc.contributor.author Peña, Raúlca
- dc.contributor.author Urtreger, Alejandro J.ca
- dc.contributor.author Diament, Miriam J.ca
- dc.contributor.author Joffé, Elisa D. Bal de Kierca
- dc.contributor.author Pijuan Andujar, Laraca
- dc.contributor.author García de Herreros, Antonioca
- dc.contributor.author Barreiro Portela, Estherca
- dc.date.accessioned 2017-01-25T11:20:18Z
- dc.date.issued 2016
- 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.ca
- 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/pdfca
- 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: 10.2174/1381612822666160623065523ca
- dc.identifier.doi http://dx.doi.org/10.2174/1381612822666160623065523
- dc.identifier.issn 1381-6128
- dc.identifier.uri http://hdl.handle.net/10230/27984
- dc.language.iso engca
- dc.publisher Bentham Science Publishersca
- 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/10.2174/1381612822666160623065523ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.subject.other Pulmons -- Càncerca
- dc.subject.other Càncer -- Tractamentca
- dc.title Pharmacological approaches in an experimental model of non-small cell lung cancer: Effects on tumor biology.ca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/acceptedVersionca