Wogonoside exerts potential anti-tumor activity against bladder cancer in vivo and in vitro via regulation of GSK3β/ERK/AKT signaling pathway

Abstract

Purpose: To explore the antitumor activity of wogonoside on bladder cancer, and its underlying mechanism of action.
 Methods: Methyl thiazolyl tetrazolium (MTT) assay was applied to determine the anti-proliferative activity of wogonoside (2 - 128 μM) on bladder cancer 5637 cell line at various times, and the halfmaximal inhibitory concentration (IC50) was measured. The antitumor activity of wogonoside (30 mg/kg, ip) against bladder cancer 5637 cell line was evaluated in nude mice bearing human bladder cancer 5637 cells. Additionally, western blotting and enzyme-linked immunosorbent assay (ELISA) were carried out to investigate the levels of the caspase-3, caspase-9, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X-protein (Bax), phosphorylated (p)-glycogen synthase kinase (GSK)-3β, p-extracellular signal-regulated kinases (p-ERK), and p-(protein kinase B) AKT.
 Results: The in vitro results revealed that wogonoside exerted anti-proliferative activity against bladder cancer 5637 cells with an IC50 of 20.59 μM (p < 0.01), in a concentration- and time-dependent manner. Furthermore, wogonoside treatment also significantly suppressed tumor volume in mice (p < 0.01). The potential mechanisms were mainly associated with apoptosis mediated by mitochondria via upregulation of caspase-3, caspase-9, and Bax levels and down-regulation of Bcl-2, p-GSK-3β, p-ERK, and p-AKT.
 Conclusion: The results reveal that wogonoside has remarkable anti-tumor potentials against bladder cancer. Further translational studies are warranted to test the clinical application of this medicinal agent in bladder cancer.