Differentiation treatment by all-trans retinoic acid reduces phenotype of glioma stem cells

Abstract

To explore the effects of all-trans retinoic acid (ATRA) on glioma stem cell phenotype. The glioma stem cell (GSC) from surgically resected human glioma specimens were isolated and enriched by neurosphere assay and then its differentiation was induced with all-trans retinoic acid (ATRA, 1 µmol/L) for 1 week. Markers were determined by flow cytometry, Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Side population cells were analyzed by flow cytometry. Growth characteristics were detected by neurosphere formation assay and cell cycle analysis. GSC and the differentiated cells (1×10(5)) were implanted stereotactically and intracranially into the Balb/c nude mice to compare the survival time. All data were analyzed with the SPSS software version 17.0. ATRA potently induced the differentiation of GSC and reduced glioma stem cell phenotype. And there were an elevated expression of glial fibrillary acidic protein (GFAP) and a reduced expression of such stem cell makers as CD133 and Nestin. The side population rate decreased. ATRA inhibited the neurosphere formation of GSC and induced the arrest of cell growth. ATRA could prolong the survival time. GSC may be differentiated efficiently by ATRA. The phenotype of GSC decreases obviously after the differentiation of ATRA and the survival time is prolonged. Thus ATRA may be applied for targeted therapies of glioma stem cell.