Effect of astrocyte elevated gene-1 on the proliferation, apoptosis and stemness of gastric cancer stem cells

ObjectiveTo investigate the expression level and effects of astrocyte elevated gene-1(AEG-1) in gastric cancer stem cells.

MethodsThe expression levels of AEG-1 mRNA and protein in gastric stem cell lines(HGC-27 and MKN-45) were detected using RT-PCR and Western blotting, respectively.The AEG-1 was processed using transient transfection, and the cells proliferation and its mechanism were investigated using the MTS assay and cell-cycle analysis.The apoptosis was examined using the activities of Caspase-3/7 and annexin V, the effect of silencing AEG-1 on the stemness of gastric stem cells was evaluated using the tumorsphere formation assay, and the tumor formation experiment was conducted to evaluate the effects of AEG-1 on the tumorigenesis of gastric stem cells in nude mice.

ResultsThe expression level of AEG-1 in gastric stem cells was higher than that in non-stem cells(P < 0.01).Cancer stem cells transfected with AEG1-siRNA resulted in the cancer stem cell cycle arrest in G₁ phase, and could significantly inhibit the cell proliferation(P < 0.01).The results of Annexin V and Caspase-3/7 activities detection showed that the knockdown of AEG-1 could induce the apoptosis of gastric stem cells.The low level of AEG-1 could significantly inhibit the ability of gastric cancer stem cells to form into balls.The loss of AEG-1 inhibited the tumorigenesis of tumor stem cells in vivo.

ConclusionsThe silencing expression of AEG-1 can suppress the cell proliferation, induce the cell cycle arrest in G₁ phase and apoptosis of gastric cancer stem cells, inhibit the tumorigenesis, which plays a positive role in tumorigenesis of gastric cancer stem cells.