ANXA1, which can bind
phospholipid in a
calcium dependent manner, is reported to play a pivotal role in
tumor progression. However, the role and mechanism of ANXA1 involved in the occurrence and development of
malignant glioma are still not well studied. Therefore, we explored the effects of ANXA1 on normal astrocytes and
glioma cell proliferation, apoptosis, migration and invasion and the underlying mechanisms. We found that ANXA1 was markedly up-regulated in
glioma cell lines and
glioma tissues. Down-regulation of ANXA1 inhibited normal astrocytes and
glioma cell proliferation and induced the cell apoptosis, which suggested that the consequences of loss of
Annexin 1 are not specific to the
tumor cells. Furthermore, the siRNA-ANXA1 treatment significantly reduced
tumor growth rate and
tumor weight. Moreover, decreasing ANXA1 expression caused G2/M phase arrest by repressing expression levels of cdc25C, cdc2 and
cyclin B1. Interestingly, ANXA1 did not affect the expressions of β-
catenin, GSK-3β and NF-κB, the key signaling molecules associated with
cancer progression. However, siRNA-ANXA1 was found to negatively regulate phosphorylation of AKT and the expression and activity of MMP2/-9. Finally, the decrease of cell proliferation and invasiveness induced by ANXA1 down-regulation was partially reversed by combined treatment with AKT agonist
insulin-like growth factor-1 (IGF-1). Meanwhile, the inhibition of
glioma cell proliferation and invasiveness induced by ANXA1 down-regulation was further enhanced by combined treatment with AKT inhibitor
LY294002. In summary, these findings demonstrate that ANXA1 regulates proliferation, migration and invasion of
glioma cells via PI3K/AKT signaling pathway.