| ObjectiveBladder Cancer(BC)is one of the most common malignancies of the urinary system.Surgery supplemented with platinum drug chemotherapy is considered to be main plan candidates for BC treatment.Cisplatin(Cis)has a broad spectrum of anti-tumor that makes it an important chemotherapy drug for the treatment of transitional cell.However,its side effects and drug resistance lead it poor prognosis for patients.It is particularly important to find a certain type of new drug to reduce the side effects of surgery and chemotherapy for BC.Sanguinarine(Sang),a benzophenanthridine alkaloid,has been previously demonstrated to exert antimicrobial,anti-inflammatory,and anti-tumor activities.Sang as a potential drug candidate may be an effective drug for BC treatment.Sang and its combined with Cis can promote the apoptosis of bladder cancer cells and inhibit tumor growth.The purpose was to clarify the chemotherapy effect of Sang on bladder cancer and to explore whether Sang has the function of reducing toxicity and enhancing the effect of Cis chemotherapy.Methods1)CCK-8 method was used to detect the proliferation of bladder cancer EJ cells treated with different concentrations of Sang with the IC50 values calculated.2)Cell migration in each group was observed by cell scratch experiments.3)Annexin V FITC/PI method was used to detect cell apoptosis in the control group,Sang group,Cis group and the combined group.4)The flow cytometer was used to detect cell cycle arrested.5)The Western blot was used to detect the influence of Bcl-2 expression in the control group,Sang group,Cis group and the combined group.6)Subcutaneous tumor-forming model of nude mice was established,Saline,Sang,Cis,and combined group were injected into caudal vein respectively.Observe the status of mice one week after the last treated.During the experiment,the survival state of the nude mice was observed,and the tumor inhibition rate and HE staining were detected to observe the pathological changes.Tumor cell apoptosis,blood biochemical parameters,blood routine indexes and HE staining pictures of important organs were observed by TUNEL staining to evaluate the biosecurity of the combined group.In the animal level,the combined group promoted the apoptosis of bladder cancer EJ cells.ResultsSang could inhibit the proliferation of EJ cells.Compared with the control group,the cell scratch healing ability was weakened and the cell migration ability was inhibited in the Sang group and the combined group.The apoptosis of cells in Sang group and combined group was significant(P<0.05),and more cells were arrested in G2/M phase.The expression of Bcl-2 in the combined group was significantly decreased(P<0.001).In the subcutaneous tumor-formation model of nude mice,compared with the control group,the tumor growth was significantly slowed(P<0.001),the apoptosis of tissue cells was significantly increased(P<0.05),and the anti-tumor effect was significant.In terms of drug safety assessment,the toxic and side effects of the Sang group and the combined group had good biosafety.Conclusion1)Sang group and combined group can inhibit cell proliferation and migration,cell cycle arrested,and induce cell apoptosis by decreasing the expression of Bcl-2.2)The combined group can reduce the toxicity and increase the efficacy of Cis chemotherapy.combined group prevent the DNA-damaged tumor cells more in the G2/M phase and thus promote cell apoptosis.In addition,the Sang has higher biological safety and less side effects.It is expected to provide experimental data support for the clinical application of bladder cancer chemotherapy,and provide reference for the development of new chemotherapy drug combined for bladder cancer.Fig[24]Table[5]Reference[60]. |
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