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


Jiexiang Chen
Yong Cao
Yan Li
Li Tang
Xiaolan Yu
Jiyi Xia

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 evaluate the anti-proliferative activity of wogonoside (2 - 128 μM) against bladder cancer 5637 cell line at different times, and the half maximal inhibitory concentration (IC50) was measured. The antitumor activity of wogonoside (30 mg/kg, i.p.) against bladder cancer 5637 cell line was confirmed via in vivo experiments on nude mice bearing human bladder cancer 5637 cells. Additionally, western blotting assay and enzyme-linked immunosorbent assay (ELISA) were used to investigate expression levels of 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 reveal that wogonoside has remarkable anti-proliferative activity against bladder cancer 5637 cells with IC50 of 20.59 μM, in a concentration-and time-dependent manner. Furthermore, wogonoside treatment also suppressed tumor volume of nude mice bearing bladder cancer 5637 cell (p < 0.01). The potential mechanisms seems to be mainly associated with apoptosis mediated by mitochondria via up-regulation of caspase-3, caspase-9, and Bax levels, and downregulation of Bcl-2, p-GSK-3β, p-ERK, and p-AKT.


Conclusion: The results reveal that wogonoside possesses anti-tumor potentials against bladder cancer. Further translational studies are warranted to test the clinical application of this medicinal agent in bladder cancer.


Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996