Combined inhibition of RAC1 and Bcl-2/Bcl-xL synergistically induces glioblastoma cell death through down-regulation of the Usp9X/Mcl-1 axis

摘要: Anti-apoptotic and pro-migratory phenotypes are hallmarks of neoplastic diseases, including primary brain malignancies. In this work, we examined whether reprogramming the apoptotic migratory machineries through a multi-targeting approach would induce enhanced cell death inhibition capacity glioblastoma cells. Preclinical testing molecular analyses combined Bcl-2/Bcl-xL RAC1 were performed in established, cultured stem-like systems. We found that resulted synergistic pro-apoptotic anti-migratory effects broad range different At level, led to decreased expression deubiquitinase Usp9X, followed by stability Mcl-1. also significantly activity tumor formation cells on chorion allantoic membranes chicken embryos was markedly impaired following inhibition. Our data indicate concomitant induces as well anti-neoplastic activities. The clinical efficacy inhibitory therapeutic strategy warrants further evaluation.