Abstract
BACKGROUND: The 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. METHODS: Guizhi 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. RESULTS: Our 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. CONCLUSIONS: Our results provide experimental evidence to support GFW as a strong candidate for intravesicle chemotherapy against bladder cancer.