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.

据报道，可以以钙依赖性方式结合磷脂的 ANXA1 在肿瘤进展中起关键作用。然而，ANXA1在恶性胶质瘤发生发展中的作用和机制仍未得到很好的研究。因此，我们探讨了ANXA1对正常星形胶质细胞和胶质瘤细胞增殖、凋亡、迁移和侵袭的影响及其潜在机制。我们发现 ANXA1 在胶质瘤细胞系和胶质瘤组织中显着上调。ANXA1 的下调抑制了正常星形胶质细胞和胶质瘤细胞的增殖并诱导了细胞凋亡，这表明 Annexin 1 缺失的后果并不是肿瘤细胞特有的。此外，siRNA-ANXA1 治疗显着降低了肿瘤生长速率和肿瘤重量。而且，降低 ANXA1 表达通过抑制 cdc25C、cdc2 和 cyclin B1 的表达水平导致 G2/M 期停滞。有趣的是，ANXA1 不影响与癌症进展相关的关键信号分子 β-catenin、GSK-3β 和 NF-κB 的表达。然而，发现 siRNA-ANXA1 负调控 AKT 的磷酸化以及 MMP2/-9 的表达和活性。最后，通过与 AKT 激动剂胰岛素样生长因子-1 (IGF-1) 联合治疗，ANXA1 下调诱导的细胞增殖和侵袭性的降低被部分逆转。同时，通过与AKT抑制剂LY294002联合治疗，进一步增强了ANXA1下调诱导的胶质瘤细胞增殖和侵袭的抑制作用。总之，这些发现表明 ANXA1 调节增殖，