Abstract

Brain tumor stem cells (BTSCs) are a small population of cancer cells that exhibit self-renewal, multi-drug resistance, and recurrence properties. We have shown earlier that peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists inhibit the expansion of BTSCs from T98G and U87MG glioma in culture. In this study, we demonstrate the influence of PPAR gamma agonists on the expression of stemness and differentiation genes in BTSCs. We have isolated BTSCs from T98G and DB29 glioma cells and cultured in NBM with B27 in the presence of EGF and bFGF. WST-1 and 3H thymidine uptake assays showed that PPAR gamma agonists, ciglitazone and 15-deoxy- ∆12,14-ProstaglandinJ2 (15d-PGJ2), inhibit viability and proliferation of T98G and DB29-BTSCs in culture. Immunostaining and flow cytometry analyses showed that PPAR gamma agonists inhibit the expansion of CD133+ BTSCs in T98G and DB29 glioma. Gene array and qRT-PCR analyses revealed that ciglitazone alters the expression of many stemness and differentiation genes in BTSCs. Further analyses confirmed that PPAR gamma agonists inhibit the expression of stemness gene Sox2 while enhancing Nanog in BTSCs. These findings highlight that PPAR gamma agonists inhibit the growth and expansion of BTSCs by altering the expression of Sox2, Nanog, and other stemness and differentiation genes. Thus, targeting stemness genes in BTSCs could be a novel strategy in the treatment of glioblastoma.