Luteolin (Lut) can inhibit the growth of various tumor cells,but its effect on the biological behavior of breast cancer cells remains unclear.The purpose of this study was to investigate the effect of Lut on the proliferation and invasion of breast cancer cells and its mechanism.Firstly,breast cancer cells (MDA-MB-231 and MCF7) were cultured in vitro,and the expression levels of ribosomal protein S12 (RPS12) at resting state were detected by western blotting.MTT assay and Western blotting were also used to measure the cell proliferation,the expression of RPS12 and c-Myc,and the phosphorylation of PI3K/Akt,mTOR and S6K.At the same time,c-Myc,PI3K/Akt and mTOR inhibitors were used to detect the cell proliferation,RPS12 and c-Myc expression.Subsequently,RPS12 promoter reporter gene was constructed to study the influence of Lut on its transcription.Finally,intracellular overexpression of c-Myc or siRNA silencing of RPS12 was performed to detect changes in cell invasion and migration.The results showed that RPS12 was highly expressed in both MDA-MB-231 and MCF7 cells.After treatment with different concentrations of Lut,the cell proliferation was significantly decreased,and the phosphorylation of PI3K/Akt,mTOR and S6K were decreased.The expressions of c-Myc and RPS12 were also significantly inhibited.Similar results were also observed for treatment of PI3K/Ak and mTOR inhibitors.In addition,inhibition of c-Myc could significantly reduce the expression and transcriptional activity of RPS12 in breast cancer cells,but the expression of RPS12 was significantly increased after overexpression of c-Myc,while silence of RPS12 could significantly inhibit the invasion and migration of breast cancer cells.These results suggest that Lut can inhibit the proliferation and invasion of MDA-MB-231 breast cancer cells,and the mechanism may be mediated by the inhibition of PI3K/Akt/mTOR signaling pathway,thus down-regulation of the c-Myc,and ultimately inhibiting the expression of RPS12.