Oridonin Suppresses Bladder Cancer Growth and Metastasis by Inducing S-Phase Arrest and Apoptosis

Bladder cancer (BC) remains a major clinical challenge owing to limited therapeutic options and high recurrence rates. Oridonin (ORI), a natural diterpenoid derived from Rabdosia plants, exhibits promising anti-tumor activity, but its effects and mechanisms in BC remain poorly defined. We evaluated the anti-BC potential of ORI in vitro and in vivo using proliferation, migration, invasion, cell-cycle, and apoptosis assays, integrated transcriptomic and proteomic analyses, Western blotting, and a 5637 xenograft model. ORI dose- and time-dependently inhibited 5637 and T24 cell proliferation, induced S-phase arrest (from 23.37% to 42.12% in 5637 and from 31.87% to 50.28% in T24; p < 0.01), and reduced migration (from 53.39% to 13.77% and from 59.81% to 12.49%; p < 0.0001) and invasion (from 74.42% to 25.43% and from 67.03% to 30.12%; p < 0.001). Multi-omics analyses revealed widespread changes enriched in apoptosis- and cell-cycle-related pathways. Consistently, ORI promoted apoptosis and necrosis, up-regulating BAX, CASP3, BID, and CYCS and down-regulating BCL2, validating the omics findings. In vivo, ORI (20 mg/kg, daily gavage) significantly suppressed xenograft growth (p < 0.001) without obvious toxicity, indicating that ORI inhibits BC growth and metastasis by inducing S-phase arrest and apoptosis and is a promising candidate for BC therapy.