Aberrant Wnt/β-catenin signaling contributes to the development of many cancers, 
including glial tumorigenesis. While cross talk between the Wnt/β-catenin and 
PI3K/AKT signaling pathways has been proposed, the impact of PI3K/AKT inhibition 
on β-catenin signaling in glioma remains unknown. In the present study, we 
report decreased cell proliferation and invasive ability upon the 
LY294002-induced inhibition of PI3K in both U251 and LN229 human glioblastoma 
cells in vitro. Pharmacologic inhibition of PI3K resulted in the downregulation 
of several members of the β-catenin pathway, including Fra-1, c-Myc, and cyclin 
D1. Downregulation impacted β-catenin-mediated transcription, as LY294002 
decreased β-catenin/TCF transcriptional activity, determined by the reporter 
assay. Similar results were observed in vivo, as intratumoral injection of 
LY294002 downregulated the expression of the components of the β-catenin pathway 
and delayed tumor growth in nude mice harboring subcutaneous LN229 xenografts. 
These results suggest that the PI3K/AKT signaling pathway regulates glioma cell 
proliferation, in part via repression of the Wnt/β-catenin pathway.