Impairment of Glioma Stem Cell Survival and Growth by a Novel Inhibitor for Survivin–Ran Protein Complex

摘要: Purpose: Glioblastoma multiforme (GBM) is a devastating disease. Recent studies suggest that the stem cell properties of GBM contribute to development therapy resistance. Experimental Design: The expression Survivin and Ran was evaluated by immunohistochemistry with tissues, quantitative reverse transcriptase (qRT)-PCR immunocytochemistry patient-derived sphere cultures. With computational structure-based drug design, 11 small-molecule compounds were designed, synthesized, as inhibitor candidates for molecular interaction protein. mechanism lead compound, LLP-3, determined Western blot, ELISA, in situ proximity ligation assay, immunocytochemistry. effects LLP-3 treatment on GSCs both vitro vivo . Quantitative carried out compare tissues from 44 newly diagnosed 31 recurrent post-chemoradiation patients. Lastly, sensitivities temozolomide-resistant spheres Results: strongly expressed particularly perivasculature, also GSC disrupted Survivin–Ran protein complex cancer cells abolished growth This inhibition dependent caspase activity associated p53 status cells. Immunohistochemistry showed significantly increased compared tumors, exhibited high treatment. Conclusions: Disruption abolishes survival , indicating an attractive novel therapeutic approach GBM. Clin Cancer Res; 19(3); 631–42. ©2012 AACR