七氟醚调控AKT/FOXO1通路对骨肉瘤细胞增殖、凋亡及化疗敏感性的影响  

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

作　　者：张光恒 鲁纲 ZHANG Guangheng;LU Gang(Department of Wound Repair Vascular Surgery,Liyuan Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430077,China;Department of General Surgery,Liyuan Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430077,China)

机构地区：[1]华中科技大学同济医学院附属梨园医院创面修复血管外科,武汉430077 [2]华中科技大学同济医学院附属梨园医院普外科,武汉430077

出　　处：《中国细胞生物学学报》2025年第4期803-811,共9页Chinese Journal of Cell Biology

摘　　要：该文探讨七氟醚(SEVO)调节蛋白激酶B(AKT)/叉头框转录因子O亚族1(FOXO1)通路对骨肉瘤(OS)细胞增殖、凋亡及化疗敏感性的影响。将体外培养人OS细胞MG63随机分为Control组(常规培养)、L-SEVO组(2%SEVO)、M-SEVO(4%SEVO)、H-SEVO组(8%SEVO)、SC79组(8%SEVO+5μmol/L AKT激动剂SC79)。甲基噻唑基四唑(MTT)与平板克隆实验检测各组细胞的增殖情况;MTT检测各组细胞的顺铂半抑制浓度(IC_(50)值);划痕实验检测各组细胞的迁移情况;Transwell实验检测各组细胞的侵袭情况;流式细胞术检测各组细胞的凋亡率;Western blot检测各组细胞中凋亡相关蛋白(Bcl-2、Bax)、AKT/FOXO1通路相关蛋白(p-AKT、AKT、p-FOXO1、FOXO1)、多药耐药相关蛋白1(MRP1)的表达情况。结果显示,与Control组相比, L-SEVO组、M-SEVO组、H-SEVO组MG63细胞的存活率、克隆数、划痕愈合率、侵袭数、Bcl-2、p-AKT/AKT、p-FOXO1/FOXO1、MRP1、IC_(50)值水平依次降低,而细胞凋亡率、Bax水平依次升高(P<0.05);与H-SEVO组相比, SC79组MG63细胞的存活率、克隆数、划痕愈合率、侵袭数、Bcl-2、p-AKT/AKT、p-FOXO1/FOXO1、MRP1、IC_(50)值水平升高,而细胞凋亡率、Bax水平降低(P<0.05)。以上结果表明, SEVO可能通过抑制AKT/FOXO1通路,抑制OS细胞MG63的细胞增殖、迁移、侵袭,促进凋亡发生,并增强其对顺铂的化疗敏感性。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+5μmol/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 ICso(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 ICso 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 ICso 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.

关 键 词：七氟醚 蛋白激酶B/叉头框转录因子O亚族1通路 骨肉瘤 细胞增殖 细胞凋亡 化疗敏感性 

分 类 号：R738.1[医药卫生—肿瘤]