title: High cofilin-1 levels correlate with cisplatin resistance in lung adenocarcinomas.
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.
authors.affiliation: Laboratório de Bioquímica Celular, Departamento de Bioquímica, ICBS/UFRGS, 2600 Ramiro Barcelos St, 90035-003, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Matheus
authors.initials: M
authors.lastname: Becker
authors.forename: Marco Antônio
authors.initials: MA
authors.lastname: De Bastiani
authors.forename: Carolina Beatriz
authors.initials: CB
authors.lastname: Müller
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Markoski
authors.forename: Mauro Antônio A
authors.initials: MA
authors.lastname: Castro
authors.forename: Fábio
authors.initials: F
authors.lastname: Klamt
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D051338:Cofilin 1 / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011379:Prognosis
chemical_list: D051338:Cofilin 1; D002945:Cisplatin
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