To investigate the chemopreventive mechanism of shikonin(SK) on endometrial cancer based on the nuclear factor E2-related factor 2(Nrf2)/quinone oxidoreductase-1(NQO1) signaling pathway.Methods:In vitro experiments were conducted to detect the inhibitory effect of SK on human endometrial cancer cells(Ishikawa) with the methylthiazolyl tetrazolium(MTT) method.The Western blotting assay was used to detect the effects of SK on NQO1，Nrf2，and γ-glutamyl cysteine synthetase(γGCS) protein expression levels.In vivo experiments were conducted to construct an animal model of endometrial cancer Ishikawa cell transplanted tumor in nude mice.The model mice were divided into a SK group，a megestrol group，and a control group.The tumor inhibition rate of each group was calculated，and the Real-time polymerase chain reaction(RT-PCR) was used to detect the mRNA expression levels of NQO1，Nrf2，and phosphatidylinositol 3-kinase(PI3K) in tumor tissues.Results:In vitro experiments showed that SK inhibited the proliferation of Ishikawa cells in a time-and concentration-dependent manner(P<0.05) and promoted the expression of proteins related to the Nrf2/ARE signaling pathway under the estrogenic environment.In vivo results indicated that the SK group could inhibit the growth of transplanted tumors in Ishikawa cells.The results of RT-PCR showed that SK could activate the PI3K/AKT signaling pathway in vivo.Conclusion:SK is involved in the activation of the Nrf2/NQO1 signaling pathway in endometrial cancer Ishikawa cells，which plays a chemopreventive role in the occurrence of endometrial cancer by preventing estrogen redox reactions.