Herein, we observed a significant decrease expression level of total PI3K-p85, p-PI3K-p85, total Akt, p-Akt, GSK-3β and p-GSK-3β, as well as their downstream, β-catenin, c-Myc and cyclin D1 after treatment with Chr-A at different concentrations for 48 h in U251 and U87-MG cells, suggesting that Chr-A could downregulate PI3K-activated Akt followed by downregulation of GSK-3β, thus attenuating expression of β-catenin and downstream, c-Myc, cyclin D1, slug, MMP2 and MMP9 to inhibit proliferation and the EMT process of human glioblastoma cells. The gene discussed is MMP2; the disease is glioblastoma.