Abstract
5-FU is a chemotherapy drug commonly used for the treatment of human cancers; however drug resistance represents a major challenge for its clinical application. In the present study, we reporte that rpL3 induced by 5-FU treatment in Calu-6 cells represses CBS transcription and reduces CBS protein stability leading to a decrease of CBS protein levels. rpL3 also regulates negatively the activation of NFκB by preventing NFκB nuclear translocation through IκB-α up-regulation. Furthermore, we demonstrate that rpL3 significantly enhances the apoptosis of 5-FU treated Calu-6 cells promoting the overexpression of the pro-apoptotic proteins Bax and the inhibition of the anti-apoptotic protein Bcl-2. We finally demonstrate that rpL3 potentiates 5-FU efficacy inhibiting cell migration and invasion. Our results suggest that combination of rpL3 and 5-FU is a promising strategy for chemotherapy of lung cancers lacking functional p53 that are resistant to 5-FU.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antimetabolites, Antineoplastic / pharmacology*
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Apoptosis / drug effects
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Apoptosis / genetics
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Cystathionine beta-Synthase / antagonists & inhibitors
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Cystathionine beta-Synthase / genetics*
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Cystathionine beta-Synthase / metabolism
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Epithelial Cells / pathology
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Fluorouracil / pharmacology*
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Gene Expression Regulation, Neoplastic*
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Humans
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Lung Neoplasms / drug therapy
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Mutation
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / genetics*
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NF-kappa B / metabolism
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Ribosomal Protein L3
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Ribosomal Proteins / agonists
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Ribosomal Proteins / genetics*
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Ribosomal Proteins / metabolism
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Signal Transduction
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Tumor Suppressor Protein p53 / genetics*
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Tumor Suppressor Protein p53 / metabolism
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bcl-2-Associated X Protein / agonists
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bcl-2-Associated X Protein / genetics
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bcl-2-Associated X Protein / metabolism
Substances
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Antimetabolites, Antineoplastic
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BAX protein, human
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BCL2 protein, human
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NF-kappa B
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Proto-Oncogene Proteins c-bcl-2
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RPL3 protein, human
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Ribosomal Protein L3
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Ribosomal Proteins
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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NF-KappaB Inhibitor alpha
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Cystathionine beta-Synthase
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Fluorouracil