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.
Highlights
IntroductionOne of the most frequently occurring tumors in men, is a leading cause of cancer deaths among people [1,2,3]
Bladder cancer, one of the most frequently occurring tumors in men, is a leading cause of cancer deaths among people [1,2,3]
These findings reveal that the anti-proliferative effects of wogonoside on bladder cancer 5637
Summary
One of the most frequently occurring tumors in men, is a leading cause of cancer deaths among people [1,2,3]. Epidemiological investigations have reported a low 5-year survival for bladder cancer. The recurrence rate of bladder cancer remains. Scutellaria baicalensis is a commonly used herbal medicine in China for treating various tumors and inflammatory diseases [9]. Wogonoside is one of the main active constituents isolated from S. baicalensis, which has been proven to possess numerous pharmacological activities by in vivo and in vitro studies. Few reports have focused on the anti-tumor effect of wogonoside. We aimed to explore the anti-tumor activity of wogonoside against bladder cancer and the potential molecular mechanisms mediating this effect
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