Abstract
BackgroundThe high risk of recurrence faced by patients with bladder cancer has necessitated the administration of supplemental intravesical chemotherapy; however, such treatments often result in severe side effects. As a result, novel intravesical agents with enhanced efficacy and minimal toxicity are urgently required for the treatment of bladder cancer.MethodsGuizhi Fuling Wan (GFW) is a traditional Chinese medicine shown to inhibit the growth of hepatocellular carcinoma. This study evaluated the growth inhibition of GFW using normal human urothelial cells and bladder cancer cells; the efficacy of GFW treatment was further compared with mitomycin C, epirubicin, and cisplatin. We also examined the progression of cell cycle and apoptosis in bladder cancer cells in response to GFW treatment. CCK-8 was employed to analyze cell viability and flow cytometry was used to study the cell cycle and apoptosis. The mechanisms underlying GFW-induced cell cycle arrest were determined by Western blot analysis.ResultsOur data demonstrate the potent inhibitory effect of GFW in the proliferation of bladder cancer cell lines, BFTC 905 and TSGH 8301. GFW presented relatively high selectivity with regard to cancer cells and minimal toxicity to normal urothelial cells. Our results also demonstrate that GFW interferes with cell cycle progression through the activation of CHK2 and P21 and induces apoptosis in these bladder cancer cells.ConclusionsOur results provide experimental evidence to support GFW as a strong candidate for intravesicle chemotherapy against bladder cancer.
Highlights
The high risk of recurrence faced by patients with bladder cancer has necessitated the administration of supplemental intravesical chemotherapy; such treatments often result in severe side effects
HPLC analysis of Guizhi Fuling Wan (GFW) Guizhi Fuling Wan is composed of five Chinese herbs, including Poria cocos, for which no accepted watersoluble bioactive component is currently available
The relative standard deviation (RSD) of these four compounds in GFW fell between 1.54-3.27% and 1.17-2.34%, (Table 1), indicating the high degree of reproducibility associated with this method
Summary
The high risk of recurrence faced by patients with bladder cancer has necessitated the administration of supplemental intravesical chemotherapy; such treatments often result in severe side effects. The most common histological type of UC is transitional cell carcinoma (TCC), which is originated from the urothelial lining of the urinary tract [3]. Guizhi Fuling Wan (GFW) is a well-known traditional Chinese herbal formula, comprising five herbs including Cinnamomi Ramulus, Poria Cocos, Paeoniae Radix Rubra, Persicae Semen, and Moutan Cortex [8]. It has been used extensively throughout Asia in the treatment of blood stasis [9,10,11]. This study compared the effects of GFW with various other chemotherapeutic agents in the growth of normal human urothelial cell and two cancer cell lines. We sought to reveal the underlying mechanisms involved in cell cycle arrest induced by GFW
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