Up-regulation of Foxp3 inhibits cell proliferation, migration and invasion in epithelial ovarian cancer

Abstract The transcription factor Forkhead Box P3 ( Foxp3 ) has been shown to play important roles in the occurring of regulatory T cells (Tregs). Limited evidence indicated that it was also expressed in tissues other than thymus and spleen, while, very recently, it was identified as a suppressor gene in breast cancer. However, the precise role and molecular mechanism of the action of Foxp3 in ovarian cancer remained unclear. To elucidate the function of Foxp3 , we examined the expression of Foxp3 in ovarian cancerous cells and the consequences of up-regulation of Foxp3 in epithelial ovarian cancer cell lines, respectively. By multiple cellular and molecular approaches such as gene transfection, CCK-8 assay, flow cytometry, RT-PCR, in-cell western, wound healing assay, and invasion assay, we found that Foxp3 was weakly/no expressed in ovarian cancerous cells. Up-regulation of Foxp3 inhibited cell proliferation, decreased cell migration, and reduced cell invasion. Compared with control, Foxp3 up-regulated cells showed decreased expression of Ki-67 and cyclin-dependent kinases ( CDKs ). Moreover, up-regulation of Foxp3 reduced the expression of matrix metalloproteinase -2 ( MMP-2 ) and urokinase-type plasminogen activator ( uPA ), resulting in the inhibition of cell migration and invasion. In addition, Foxp3 up-regulation inhibited the activation of mammalian target of rapamycin (mTOR) and NF-κB signaling. These findings suggested that up-regulation of Foxp3 could be a novel approach for inhibiting ovarian cancer progression.