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

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.