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

NI Xin¹, LI Yanchun², ZHANG Qionghui³, XU Xiaofeng^4
*

( ¹ Department of Anesthesiology, Jiading District Central Hospital Affliated Shanghai University of Medicine & Health Sciences, Shanghai 201800, China; ² Department of Obstetrics and Gynecology, Nanxiang Branch of Ruijin Hospital, Shanghai 201802, China; ³ Department of Women’s Health, Community Health Service Center of Xuhang Town, Jiading District, Shanghai 201808, China; ⁴ Department of Obstetrics and Gynecology, Jiading District Central Hospital Affliated Shanghai University of Medicine &Health Sciences, Shanghai 201800, China)

Abstract:

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 (5 μmol/L), M-ursolic acid group (10 μmol/L), H-ursolic acid group (20 μmol/L), and FKBP38 inhibitor FKBP51-Hsp90-IN-1 (0.1 μmol/L)+H-ursolic acid (20 μmol/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.

CSTR: 32200.14.cjcb.2025.02.0006