Effects of transforming growth factor-β inhibitor on the proliferation of glioma stem/progenitor cell.

Transforming growth factor-β (TGF-β) signaling pathways play an important role in inhibition and promotion of cell proliferation in neural stem cells (NSCs) and glioma stem/progenitor cells (GSPCs), respectively. However, the mechanisms underlying these processes remain unknown. We presumed that there may be functional inhibition at the receptor downstream of TGF-β signaling pathway leading to the activation of non- TGF-β/Smad signaling pathway, which stimulates the proliferation of GSPCs. In this study, GSPCs, from glioma cell lines SHG44, were cultivated with TGF-β receptor inhibitors (LY2157299 and LY2109761), and then the proliferative capability of GSPCs was measured; as well, the synthesis of TGF-β ligands, and the mRNA expression level of TGF-β and some key molecules of non-Smad signaling pathways were also detected. Our results showed that inhibitors against TGF-β receptors could promote the proliferation of GSPCs, and the synthesis of TGF-β ligands was enhanced. Furthermore, the inhibition of TGF-β receptor may lead to the activation of non-Smad signaling pathways (mTOR and NF-κB). In conclusion, the down-regulation of TGF-β receptor capability by TGF-β receptor inhibitors can increase TGF-β ligands synthesis and secretion, which then promote GSPCs proliferation by activating non-Smad signaling pathways.