FOXD3 inhibits cell proliferation, migration and invasion in nasopharyngeal carcinoma through regulation of the PI3K/Akt pathway.

FOXD3 has been found previously to positively regulate miR-26b, a tumor inhibitor of nasopharyngeal carcinoma (NPC). However, its precise function and associated mechanism of action in NPC has yet been investigated. In this study, FOXD3 mRNA and protein expression was evaluated using RT-qPCR, western blotting and immunohistochemistry (IHC). Protein levels involved in the PI3K/Akt pathway were assessed by western blot and cell proliferation was determined by MTT and colony forming assays. Additionally, cell apoptosis was assessed by flow cytometric assay. Finally, the migration and invasion capabilities of the NPC cells were determined using wound healing and Transwell assays. We found that FOXD3 levels were relatively low in NPC tissue and cells, whereas its increase caused the inhibition of the PI3K/Akt pathway. Functional experiments found that overexpression of FOXD3 suppressed cell proliferation, migration and invasionand enhanced cell apoptosis in C6661 cells. IGF-1, an activator of the PI3K/Akt pathway, reversed the inhibitory effect of FOXD3. Furthermore, we found an upregulation of the PI3K/Akt pathway and inhibitory effects of FOXD3 upregulation on C6661 cellular activities. In conclusion, FOXD3 negatively mediated the PI3K/Akt pathway to restrain the processes involved in C6661 cell pathology. These findings further exposed the function and downstream axis of FOXD3 in NPC and displayed a promising new target for NPC therapy.