熊果酸通过调控FKBP38/mTOR/SREBPs信号通路对宫颈癌细胞增殖、迁移和侵袭的作用  

The Effects of Ursolic Acid on Proliferation,Migration,and Invasion of Cervical Cancer Cells through Regulating the FKBP38/mTOR/SREBPs Signaling Pathway

作　　者：倪欣 李艳春 张琼慧 徐晓锋 NI Xin;LI Yanchun;ZHANG Qionghui;XU Xiaofeng(Department of Anesthesiology,Jiading District Central Hospital Affiliated Shanghai University of Medicine&Health Sciences,Shanghai 201800,China;Department of Obstetrics and Gynecology,Nanxiang Branch of Ruijin Hospital,Shanghai 201802,China;Department of Women's Health,Community Health Service Center of Xuhang Town,Jiading District,Shanghai 201808,China;Department of Obstetrics and Gynecology,Jiading District Central Hospital Affiliated Shanghai University of Medicine&Health Sciences,Shanghai 201800,China)

机构地区：[1]上海健康医学院附属嘉定区中心医院麻醉科,上海201800 [2]上海市瑞金医院南翔分院妇产科,上海201802 [3]上海市嘉定区徐行镇社区卫生服务中心妇女保健科,上海201808 [4]上海健康医学院附属嘉定区中心医院妇产科,上海201800

出　　处：《中国细胞生物学学报》2025年第2期212-220,共9页Chinese Journal of Cell Biology

基　　金：上海市嘉定区卫生健康委员会科研项目(批准号:2022-KY-11)资助的课题。

摘　　要：该研究旨在探究熊果酸通过FK506结合蛋白38(FKBP38)/哺乳动物雷帕霉素靶蛋白(mTOR)/固醇调节元件结合蛋白(SREBPs)信号通路对宫颈癌细胞增殖、侵袭和迁移的作用。将HeLa细胞分为CK组(正常培养细胞)、L-熊果酸组(5μmol/L)、M-熊果酸组(10μmol/L)、H-熊果酸组(20μmol/L)和FKBP38抑制剂FKBP51-Hsp90-IN-1(0.1μmol/L)+H-熊果酸(20μmol/L)组。CCK-8法检测细胞活性,流式细胞术检测细胞凋亡情况,划痕实验检测细胞迁移情况,Transwell法检测细胞侵袭情况,Western blot检测Bax、Bcl-2、cleaved-Caspase-3、FKBP38、mTOR、SREBPs蛋白表达情况。L-熊果酸组、M-熊果酸组、H-熊果酸组较CK组细胞D值、划痕愈合率、侵袭细胞数以及Bcl-2、p-mTOR/mTOR、SREBPs蛋白表达水平降低,细胞凋亡率以及Bax、cleavedCaspase-3、FKBP38蛋白表达水平升高(P<0.05);FKBP51-Hsp90-IN-1+H-熊果酸组较H-熊果酸组D值、划痕愈合率、侵袭细胞数以及Bcl-2、p-mTOR/mTOR、SREBPs蛋白水平显著增加,细胞凋亡率以及Bax、cleaved-Caspase-3、FKBP38蛋白水平显著降低(P<0.05)。熊果酸可能通过调控FKBP38/mTOR/SREBPs信号通路,进而抑制HeLa细胞的增殖、迁移及侵袭等。This study aims to investigate the mechanism of action of ursolic acid in regulating the proliferation,invasion and migration of cervical cancer cells through the FKBP38(FK506-binding protein 38)/mTOR(mammalian target of rapamycin)/SREBPs(sterol regulatory element binding proteins)signalling pathway.HeLa cells were assigned into CK group(normal cultured cells),L-ursolic acid group(5μmol/L),M-ursolic acid group(10μmol/L),H-ursolic acid group(20μmol/L),and FKBP38 inhibitor FKBP51-Hsp90-IN-1(0.1μmol/L)+H-ursolic acid(20μmol/L)group.The CCK-8 assay was used to detect cell viability.Flow cytometry was used to detect cell apoptosis.The scratch assay was used to detect cell migration.The Transwell assay was used to detect cell invasion,and Western blot was used to detect the protein expression levels of Bax,Bcl-2,cleaved-Caspase-3,FKBP38,mTOR and SREBPs.The D value,scratch healing rate,number of invasive cells,the protein expression of Bcl-2,p-mTOR/mTOR,and SREBPs in the L-ursolic acid group,M-ursolic acid group,and H-ursolic acid group were lower than those in the CK group,and the apoptosis rate,the protein expression of Bax,cleaved-Caspase-3,and FKBP38 were higher(P<0.05).The D value,scratch healing rate,number of invasive cells,the protein expression of Bcl-2,p-mTOR/mTOR,and SREBPs in the FKBP51-Hsp90-IN-1+H-ursolic acid group were higher than those in the H-ursolic acid group,and the apoptosis rate,the protein expression of Bax,cleavedCaspase-3,and FKBP38 were lower(P<0.05).Ursolic acid may inhibit the proliferation,migration,and invasion of HeLa cells by modulating the FKBP38/mTOR/SREBPs signaling pathway.

关 键 词：熊果酸 FKBP38/mTOR/SREBPs通路 宫颈癌 迁移 侵袭 

分 类 号：R737.33[医药卫生—肿瘤]