Impacts of Sevoflurane on Proliferation, Apoptosis, and Chemotherapy Sensitivity of Osteosarcoma Cells by Regulating the AKT/FOXO1 Pathway

ZHANG Guangheng¹, LU Gang²*

(¹Department of Wound Repair Vascular Surgery, Liyuan Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China; ²Department of General Surgery, Liyuan Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China)

Abstract:

This study investigated the impacts of SEVO (sevoflurane) on the proliferation, apoptosis, and chemotherapy sensitivity of OS (osteosarcoma) cells by regulating the AKT (protein kinase B)/FOXO1 (forkhead transcription factor O subfamily 1) pathway. Human OS cells MG63 were cultured in vitro and randomly assigned into Control group (conventional culture), L-SEVO group (2% SEVO), M-SEVO group (4% SEVO), H-SEVO group (8% SEVO), and SC79 group (8% SEVO+5 μmol/L AKT agonist SC79). MTT (methyl thiazolyl tetrazole) and plate cloning experiments were applied to detect the proliferation in each group. MTT was applied to detect the IC50 (half maximal inhibitory concentration) of cisplatin in each group. Scratch experiment was applied to detect the migration in each group. Transwell experiment was applied to detect the invasion of various groups. Flow cytometry was applied to detect the apoptosis rate of each group. Western blot was applied to detect the expression of apoptosis related proteins (Bcl-2, Bax) and AKT/FOXO1 pathway related proteins (p-AKT, AKT, p-FOXO1, FOXO1), multidrug resistance associated protein 1 (MRP1). The results showed that compared with the Control group, the survival rate, clone number, scratch healing rate, invasion rate, Bcl-2, p-AKT/AKT, p-FOXO1/FOXO1, MRP1, and IC50 values of MG63 cells in the L-SEVO group, M-SEVO group, and H-SEVO group were reduced, while the apoptosis rate and Bax level were increased (P<0.05). Compared with the H-SEVO group, the survival rate, clone number, scratch healing rate, invasion number, Bcl-2, p-AKT/AKT, p-FOXO1/FOXO1, MRP1, and IC50 values of MG63 cells in the SC79 group were increased, while the apoptosis rate and Bax levels were decreased (P<0.05). These results suggest that SEVO may inhibit the proliferation, migration, and invasion of OS MG63 cells, promote apoptosis, and enhance its sensitivity to cisplatin chemotherapy by suppressing the AKT/FOXO1 pathway.

CSTR: 32200.14.cjcb.2025.04.0005