Mechanism of inhibitory effect of sodium aescinate on the proliferation and migration of nasopharyngeal carcinoma cells via Keap1/Nrf2/HO-1 signaling pathway
YIN Xiuwen
BAO Yongzheng
HU Zhibang
MA Jing
Abstract：Objective To investigate the effects of sodium aescinate(SA)on the proliferation and migration of nasopharyngeal carcinoma cells,as well as its regulatory mechanism on Kelch-like epichlorohydrin-related protein-1(Keap1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods CNE1 cells were treated with low and high doses of SA,the functional salvage experiment was carried out with cobalt protoporphyrin(CoPP),a HO-1 agonist.Functional recovery test with ferroptosis inhibitor Ferrostatin-1(Fer-1).3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromid(MTT)was used to detect the growth activity.Cell proliferation and apoptosis were assessed using the plate clone formation and AO/EB double staining,respectively.Transwell chamber was used to detect the cell migration.Real-time quantitative PCR(RT-qPCR)was used to detect the expression of epithelial mesenchymal transition(EMT)related genes.Western blotting was used to detect the expression levels of Keap1,Nrf2,HO-1,Gpx4,SLC7A11 and TFR1 in cells.Results SA significantly inhibited the growth,migration,and proliferation of nasopharyngeal carcinoma CNE1 cells(P<0.05).AO/EB double staining results showed that SA markedly promoted the apoptosis of CNE1 cells(P<0.05).RT-qPCR analysis revealed that SA significantly downregulated the mRNA expression of N-cadherin and Vimentin while upregulating E-cadherin mRNA expression(all P<0.05).Western blotting results demonstrated that SA notably decreased the protein expression of Nrf2,HO-1,Gpx4,and SLC7A11,and increased the expression of Keap1 and TFR1(all P<0.05).Functional rescue experiments indicated that CoPP could partially reverse the antitumor effects of SA(P<0.05).Functional recovery experiments showed that Fer-1 could partially restore the inhibitory effects of SA on cancer cell proliferation and migration(P<0.05).Conclusion SA effectively suppressed the EMT process,and reduced the proliferation and migration abilities of nasopharyngeal carcinoma CNE1 cells,which might be associated with its regulation of the Keap1/Nrf2/HO-1 signaling pathway.
Keywords：nasopharyngeal carcinomasodium aescinateproliferationapoptosismigrationkelch-like epichlorohydrin-related protein-1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway
Publication Date：2025-11-28
Online Publishing Date：2026-01-05(First online date of this platform, not the publication date of the document)
Pages：7( 1054-1060 )