Knockout of the placenta specific 8 gene radiosensitizes nasopharyngeal carcinoma cells by activating the PI3K/AKT/GSK3β pathway.

: The present study investigated the radiosensitizing effect of placenta specific 8 (PLAC8) in nasopharyngeal carcinoma (NPC) cells. A PLAC8-knockout CNE2 cell line was constructed using the CRISPR/Cas9 system. The CCK-8 assay demonstrated knockout of PLAC8 significantly reduced cell proliferation and cell survival after irradiation compared to both control cells and non-irradiated PLAC8-knockout cells. The clonogenic assay showed knockout of PLAC8 enhanced the radiosensitivity of NPC cells. Flow cytometry revealed knockout of PLAC8 increased apoptosis and G2/M phase arrest after irradiation. Western blotting demonstrated knockout of PLAC8 was associated with increased levels of γHA2X, a higher BAX:BCL-2 ratio, and increased levels of phosphorylated-Akt and phosphorylated-GSK-3β. Overall, this study indicates PLAC8 contributes to radioresistance in NPC by inhibiting the PI3K/AKT/GSK3β pathway.