Comparative transcriptomic analysis and mechanistic characterization revealed the use of formononetin for bladder cancer treatment

Bladder cancer is one of the most common cancers worldwide, with 213 000 deaths reported in 2020. Patients with a progression from non-muscle-invasive bladder cancer to muscle-invasive disease have poorer prognosis and survival rates. Therefore, there is an urgent need to identify novel drugs to prevent the recurrence and metastasis of bladder cancer. Formononetin is an active compound extracted from the herb Astragalus membranaceus that possesses anticancer properties. Few studies have demonstrated the anti-bladder cancer effects of formononetin; however, the detailed mechanism remains unknown. In this study, we used two bladder cancer cell lines, TM4 and 5637, to investigate the potential role of formononetin in bladder cancer treatment. Comparative transcriptomic analysis was conducted to delineate the molecular mechanisms underlying the anti-bladder cancer effects of formononetin. Our results showed that formononetin treatment inhibited the proliferation and colony-forming abilities of bladder cancer cells. Additionally, formononetin reduced the migration and invasion of bladder cancer cells. Transcriptomic analysis further highlighted the involvement of formononetin-mediated two clusters of genes involved in endothelial cell migration (FGFBP1, LCN2, and STC1) and angiogenesis (SERPINB2, STC1, TNFRSF11B, and THBS2). Taken together, our results suggest the potential use of formononetin to inhibit the recurrence and metastasis of bladder cancer through the regulation of different oncogenes.