摘要Pristimerin,which is one of the compounds present in Celastraceae and Hippocrateaceae,has antitumor effects.However,its mechanism of action in esophageal squamous cell carcinoma(ESCC)remains unclear.This study aims to investigate the efficacy and mechanism of pris-timerin on ESCC in vitro and in vivo.The inhibitory effect of pristimerin on cell growth was as-sessed using trypan blue exclusion and colony formation assays.Cell apoptosis was evaluated by flow cytometry.Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction(qRT-PCR),Western blotting,and immunohisto-chemistry.RNA sequencing(RNA-Seq)was employed to identify significantly differentially expressed genes(DEGs).Cell transfection and RNA interference assays were utilized to exam-ine the role of key proteins in pristimerin's effect.Xenograft models were established to eval-uate the antitumor efficiency of pristimerin in vivo.Pristimerin inhibited cell growth and in-duced apoptosis in ESCC cells.Upregulation of Noxa was crucial for pristimerin-induced apop-tosis.Pristimerin activated the Forkhead box O3a(FoxO3a)signaling pathway and triggered FoxO3a recruitment to the Noxa promoter,leading to Noxa transcription.Blocking FoxO3a re-versed pristimerin-induced Noxa upregulation and cell apoptosis.Pristimerin treatment sup-pressed xenograft tumors in nude mice,but these effects were largely negated in Noxa-KO tu-mors.Furthermore,the chemosensitization effects of pristimerin in vitro and in vivo were me-diated by Noxa.This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation.These findings suggest that pristimer-in may serve as a potent anticancer agent for ESCC treatment.