RpL3 promotes the apoptosis of p53 mutated lung cancer cells by down-regulating CBS and NF?B upon 5-FU treatment.

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 NF?B by preventing NF?B nuclear translocation through I?B-? 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.

SUBMITTER: Russo A 

PROVIDER: S-EPMC5141482 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature