The purpose of this study was to investigate the mechanism of rocaglaol (Roc) on the proliferation of breast cancer via Cyclin D1.Different concentrations of Roc were treated with human breast cancer cells MCF7 and MDA-MB-231.MTT assay were used to detect the effects of Roc on the cell proliferation.Flow cytometry technology determined the cell cycle distribution affected by Roc.Western blot analyzed the effects of Roc on Cyclin D1,as well as PCR and q-PCR were used to detect the effects of Roc on the CCND1 gene.Protease inhibitor MG132 was used to detect the way how Roc regulated Cyclin D1.The results showed that Roc inhibited the proliferation of human breast cancer cells MCF7 and MDA-MB-231,arrested the cell cycle at the G2/M phase,and down-regulated the protein expression of Cyclin D1,but did not affect the expression of CCND1 gene.MG132 could restore the decrease of Cyclin D1 expression induced by Roc,indicating that Roc regulates the expression of Cyclin D1 by proteasome degradation.The above results indicate that Roc decreases the expression of Cyclin D1 at post-transcriptional level,thereby inhibiting the proliferation of breast cancer cells.