Mechanism of AKT1 Enhancing Migration and Invasion of Epithelial Ovarian Cancer Cells

Abstract：Objective To explore the effects of AKT1 gene on the invasion and migration of epithelial ovarian cancer cells SKOV3 and its mechanism. Methods Recombinant plasmid carrying the full-length AKT1 cDNA and AKT1 shRNA plasmid were constructed. Plasmids were transfected into SKOV3 cells to dual-directionally regulate AKT1 expression. RT-PCR and western blot were used to detect the transfection efficiency. Wound healing assay was used to analyze cell migration. Transwell-Matrigel assay was used to analyze cell invasion. RT-PCR was used to explore the expression of CXCR4, VEGF, MMP-2, MMP-9 and uPA which were related with cell invasion and migration at mRNA level. Results A plasmid (pEF-1α-AKT1) containing full length of AKT1 cDNA and a specifi c AKT1-targeted shRNA expression plasmid were constructed successfully, which could effectively regulate the activation of p-AKT after SKOV3 cells transfected. Compared with untranfected cells or non-target shRNA transfected cells, up-regulation AKT1 promoted cell migration and invasion, and increased the expression of CXCR4, VEGF, MMP-2, and uPA at mRNA level(P＜0.05). On the other hand, down-regulation AKT1 inhibited cell migration and invasion, and decreased the expression of CXCR4, VEGF, MMP-2, and uPA at mRNA level(P＜0.05). Conclusion AKT1 might impact cell migration and invasion by regulating the expression of CXCR4, VEGF, MMP-2, and uPA at mRNA level.