Silencing of Astrocyte elevated gene-1 (AEG-1) inhibits proliferation, migration, and invasiveness, and promotes apoptosis in pancreatic cancer cells

To investigate the role of Astrocyte elevated gene-1 (AEG-1) in the development and progress of pancreatic cancer, short hairpin RNA (shRNA) was inserted into the RNA interference vector to knock-down the endogenous AEG-1 in two pancreatic cancer cell lines: AsPC-1 and PANC-1. Our results showed that silencing of AEG-1 suppressed the proliferation, colony formation ability, and cell sternness of AsPC-1 and PANC-1 cells, and inhibited their G1-to-S phase transition. Results from apoptosis assay showed that knock-down of AEG-1 led to cell apoptosis. The expression of ant i-apoptotic Bcl-2 was down regulated and that of the pro-apoptotic Bax and cleaved caspase-3 was upregulated in AEG-1-silenced pancreatic cancer cells. Further, the capability of AEG-1-silenced cells to migrate and to invade through the Matrigel-coated membrane was weaker, and the expression of matrix metallopeptidase 2 (MMP-2) and MMP-9 were decreased. Moreover, the AKT-beta-catenin signaling pathway was inhibited in the cells with knock-down of AEG-1. In addition, the growth of xenograft tumors formed by AsPC-1 and PANC-1 cells was suppressed by AEG-1 shRNA. In conclusion, our study demonstrates that pancreatic cancer cells require AEG-I to maintain their survival and metastasis, suggesting AEG-1 as a potential target for the treatment of pancreatic cancers.