香叶木素通过增强PIK3R1 mRNA稳定性抑制乳腺癌细胞侵袭和迁移OA

To explore the inhibitory effect and molecular mechanism of diosmetin on the invasion and mi-gration of breast cancer cells,MCF7 and MDA-MB-231 cells were treated with different doses(5 mg/L,10 mg/L,20 mg/L)of diosmetin for 24 h,and then the changes in the invasion and migration abilities of breast cancer cells were detected using the Transwell assay and cell scratch healing assay.The effect of diosmetin on the expression of metastasis-related proteins was further determined by Western-blot.The Gene Expression Om-nibus(GEO)database was used to analyze differentially expressed genes in breast cancer tissues,and the HERB database was used to obtain the regulatory targets of diosmetin.The effect of diosmetin on the ex-pression of phosphatidylinositol 3-kinase,regulatory subunit 1(PIK3R1)was confirmed by real-time fluores-cent quantitative PCR(qRT-PCR)and Western-blot experiments.Finally,actinomycin D was used to deter-mine the effect of diosmetin on the stability of PIK3R1 mRNA.The results showed that diosmetin signifi-cantly inhibited the invasion and migration ability of breast cancer cells in a dose-dependent manner(P＜0.05).Furthermore,in a dose-dependent manner,diosmetin significantly increased the levels of E-cadherin and significantly decreased the levels of N-cadherin and matrix metallopeptidase 2(MMP2).Additionally,PIK3R1 was both a differentially expressed gene in breast cancer and a target of diosmetin.Breast cancer patients with low levels of PIK3R1 had a worse disease-free survival(P＜0.05).Treatment with diosmetin significantly up-regulated the levels of PIK3R1 mRNA and protein(P＜0.05),and also significantly improved the stability of PIK3R1 mRNA.These results indicate that diosmetin can inhibit the invasion and migration of breast cancer cells,which may be achieved by increasing the stability of PIK3R1 mRNA.