Objective Soy isoflavones have been attracted much attention in the chemoprevention of human cancer including breast,prostate and colon cancer,and recently were confirmed as natural ligands for PPARγ.However,the relationship between the PPARγ signaling pathway and the anti-cancer effects of soy isoflavones have not been clarified yet.Methods and Results Human cancer cell line,MCF-7,DU-145 and HT-29 were used to investigate the role of PPARγ signaling pathway in the anti-cancer effects of soy isoflavones.The cancer cells were treated with genistein,daidzein alone or in combination with GW9662,a specific PPARγ inhibitor.The expression and transcriptional activity of PPARγ were measured by immunocytochemieal staining and PPRE-driven luciferase reporter gene assay respectively,and the proliferation of cancer cells was measured by CCK-8 assay.We found that PPARγ mainly distributed in the cytoplasm of untreated cancer cells,after treatment with genistein or daidzein PPARy translocated to nucleus,meanwhile the luciferase activities also significantly increased,but these effects induced by soy isoflavones could be reversed by GW9662.We also showed that genistein and daidzein inhibited the proliferation of cancer cells in a dose and time dependent manner,but the inhibitory effects of genistein and daidzein could be blocked by GW9662 significantly.Conclusion Taken together,activation of PPARγ signaling pathway may represent a novel mechanism for the anti-cancer effects of soy isoflavones.