Salvigenin inhibits gastric cancer progression by suppressing the EGFR/PI3K/AKT pathway

Background: Salvigenin recently been shown to possess antitumor properties. However, no study has focused on the underlying relationship of salvigenin with gastric Cancer (GC). This study aimed to explore salvigenin function on GC and delineate the potential molecular mechanisms.

Methods: The effects of salvigenin on the malignant behavior of GC cells were explored using colony formation, EdU, flow cytometry, scratch as well as transwell assays. The potential mechanisms of action of salvigenin in GC were explored through network pharmacology analysis, molecular docking, Western blot, immunofluorescence staining, and rescue experiments. Besides, the in vivo effects of salvigenin on GC were assessed using a xenograft mouse model.

Results: Salvigenin could suppress the proliferative, migratory and invasive capabilities of GC cells, while facilitating Apoptosis. Furthermore, salvigenin could inactivate EGFR/PI3K/Akt pathway in AGS and HGC-27 cells. Additionally, rescue experiments using NSC 228155 and EGFR overexpression further confirmed that activating EGFR/PI3K/Akt signaling could reverse the effects of salvigenin on the malignant behavior of GC cells. In addition, salvigenin was also confirmed to repress GC tumor growth in vivo via inactivating EGFR/PI3K/Akt signaling.

Conclusion: Salvigenin might suppress the proliferative, migratory, and invasive capacity, but facilitate the apoptotic ability in GC through inactivating EGFR/PI3K/Akt signaling.

EGFR; Gastric cancer; PI3K/AKT; Salvigenin.