Effect and mechanism of cyclanoline on nitrosamine-induced bladder cancer in rats / 中草药

ABSTRACT

Objective: To investigate the effect and mechanism of cyclanoline on nitrosamine (BBN)-induced bladder cancer in rats. Methods: Male SD rats were randomly divided into control group, model group, Cyc-low dose (20 mg/kg) group, Cyc-high dose (40 mg/kg) group and cisplatin (5 mg/kg) group. Rats were intragastrically administered with 0.5 mL BBN (0.4 kg/L, twice a week for 8 weeks) to establish bladder cancer model. In addition to control and model group given with normal saline, the other groups were intraperitoneally injected with drugs (once a day for 8 weeks). The bladder tissue was collected after experiment. HE staining was used to investigate the histopathological changes of the bladder in rats. The expressions of MMP9 and Ki67 were observed by immunohistochemistry method, and the expressions of KLF4, p21, CyclinD1, E-cadherin, N-cadherin, Vimentin, Wnt, β-catenin in the bladder tissues were detected by Western bloting. Results: Compared with the model group, cyclanoline effectively inhibited the infiltration of cystitis cells, promoted the degeneration of cancer cells, and reduced the proportion of cytoplasm. Cyclanoline significantly decreased the expressions of MMP9 and Ki67 (P < 0.05, 0.01), up-regulated the expressions of KLF4, p21 and E-cadherin (P < 0.05, 0.01), down-regulated the expressions of CyclinD1, Wnt, β-catenin, N-cadherin and Vimentin in bladder cancer tissues (P < 0.05, 0.01). Conclusion: Cyclanoline promotes the expression of KLF4, inhibits Wnt/β-catenin signaling transduction and the epithelial cell-mesenchymal transition of bladder cancer cells, thereby inhibiting the migration and invasion of bladder cancer cells. Meanwhile, cyclanoline regulates the expressions of p21 and CyclinD1 by up-regulating KLF4, affects the proliferation of bladder cancer cells, and thereby delays the pathological process of BBN-induced bladder cancer in rats.