The addition of celecoxib improves the antitumor effect of cetuximab in colorectal cancer: role of EGFR-RAS-FOXM1-β-catenin signaling axis

• DOI: 10.18632/oncotarget.15567
• Publication Date: 2017-02-22T16:33:37Z
• Authors: Araceli Valverde; Jon Peñarando; Amanda Cañas; Laura M. López-Sá...; Francisco Conde; Silvia Guil-Luna; Vanessa Hernández; Carlos Villar; Cristina Morales-...; Juan de la Haba-R...; Enrique Aranda; Antonio Rodríguez...
• Keywords: Celecoxib; FOXM1

// Araceli Valverde 1 , Jon Peñarando 1, 2 Amanda Cañas Laura M. López-Sánchez Francisco Conde Silvia Guil-Luna Vanessa Hernández Carlos Villar 3 Cristina Morales-Estévez 4 Juan de la Haba-Rodríguez 2, Enrique Aranda Antonio Rodríguez-Ariza Instituto Maimónides Investigación Biomédica Córdoba (IMIBIC), Córdoba, Spain Centro Investigacion en Red Cáncer, Madrid, Unidad Gestión Clínica Anatomía Patológica, Hospital Universitario Reina Sofía, Oncología, Correspondence to: Rodríguez-Ariza, email: [e-mail] Keywords: β-catenin, colorectal cancer, COX-2, EGFR, FOXM1 Received: July 20, 2016 Accepted: January 23, 2017 Published: February 21, ABSTRACT Here we showed that the addition of COX-2 inhibitor celecoxib improved antitumor efficacy in cancer (CRC) monoclonal anti-EGFR antibody cetuximab. The augmented cetuximab to inhibit cell proliferation and induce apoptosis CRC cells. Moreover, combination was more effective than either treatment alone reducing tumor volume a mouse xenograft model. combined enhanced inhibition EGFR signaling altered subcellular distribution β-catenin. knockdown this transcription factor participates antitumoral response. Besides, decreased β-catenin/FOXM1 interaction reduced stem subpopulation cells, as indicated their diminished capacity form colonospheres. Notably, inmunodetection nuclei cells human adenocarcinomas significantly associated with response patients In summary, our study shows enhances due impairment EGFR-RAS-FOXM1-β-catenin axis. Results also support could be predictive marker mCRC therapy.