In this study, we describe the effect of a combination treatment with PPARγ ligands and its inhibitor GW9662 on spheres of glioblastoma cells through downregulation of BIS and 14-3-3 gamma levels, as well as inhibition of SOX2, MMP2 activity, and sphere-forming activity without enhancing the levels of cleaved poly(ADP-ribose) polymerase (PARP). This evidence concerns the gene SOX2 and glioblastoma.