Formononetin Inhibits Metastatic Potential of Human Prostate Cancer Cells via Upregulating EGR1

Objectives: Formononetin is a natural isoflavone compound and has been reported to have anti‑cancer properties. However, the mechanism by which formononetin inhibits hormone‑resistant prostate cancer (PCa) has not been reported. The present study investigates whether and how formononetin inhibits the epithelial‑mesenchymal transition (EMT) of hormone‑resistant PCa cell lines. Materials and Methods: The proliferation, migration and invasion of PCa cells were analyzed using RTCA system and CCK8 assays. Expression of EMT‑related markers and MAPK pathway were analyzed using quantitative reverse transcription PCR (RT‑qPCR), immunofluorescence staining and immunoblotting. Gene expression profile was observed by RNA‑sequence analysis, and the EGR1 expression analysis in human PCa tissue was referred to the Cancer Genome Atlas database and The Human Atlas Database. Results: Formononetin inhibited the rate of proliferation, migration, and invasion of PCa cells, increased protein levels of E‑cadherin, reduced protein levels of fibronectin and the phosphorylated ERK1/2 and JNK, as well as the mRNA levels of the fibronectin, slug and snail. Formononetin remarkably upregulated EGR1, as confirmed by bioinformatics analysis, RT‑qPCR and western blotting. Furthermore, the EGR1 expression was lower in human PCa tissue versus its control, and in higher Gleason grade versus the lower Gleason grade PCa. Conclusion: Formononetin could ameliorate tumor aggressiveness via reversing the EMT of hormone‑resistant PCa cells. The potential mechanisms involved are inactivation of MAPK signalling and subsequent upregulation of EGR1 expression.