The Combined Treatment of 4EGl‐1 and MK‐2206 Inhibits Nasopharyngeal Carcinoma Progress by Inducing Autophagy

ABSTRACT Nasopharyngeal carcinoma (NPC) represents a prevalent malignant neoplasm within the head and neck region. However, therapeutic outcomes for advanced‐stage NPC remain suboptimal. This study seeks to elucidate the impact of the eIF4E/eIF4G interaction inhibitor, 4EGI‐1, on NPC cellular dynamics. The effect of 4EGI‐1 on NPC cell proliferation, migration, and invasion was investigated by sulphorhodamine (SRB) assay, colony formation assay, Transwell, and scratch assay. Furthermore, the role of 4EGI‐1 on NPC cell autophagy was examined using immunofluorescent staining and western blot. Finally, the in vitro results of 4EGI‐1 were confirmed in subcutaneous nude mouse models. In vitro, cells were treated with 4EGI‐1 (12.5–100 μM) for 24 h or 48 h to select drug‐sensitive cell lines. In vivo, we established a subcutaneous xenograft mouse model of nasopharyngeal carcinoma and administered 4EGI‐1 and/or MK‐2206. 3‐MA was used to inhibit the autophagy. NPC cells treated with 4EGI‐1 exhibited a significant decrease in proliferation, migration, and invasion but an increase in autophagy compared to the control group. Additionally, MK‐2206 (AKT inhibitor) treatment reversed 4EGI‐1‐induced activation of the AKT signaling pathway and reduced the dosage of 4EGI‐1. 3‐Methyladenine (3‐MA, a selective PI3K inhibitor) treatment abrogated 4EGI‐1‐induced autophagy in NPC cells, resulting in diminished 4EGI‐1 anti‐proliferation, anti‐migration, and anti‐invasion effects. The in vitro results were confirmed with in vivo mouse models. 4EGI‐1 strongly inhibited NPC growth and metastasis, and 4EGI‐1 may develop as the potential therapy for the treatment of metastatic NPC.