| More than90%of Bladder cancer is bladder urothelial carcinoma, and non-invasive urothelialcarcinoma accounts for about70%, the rest is invasive urothelial carcinoma. Although to bladder infusionchemotherapy after TURB-t, but the recurrence rate is still high, and part of the non-invasive urothelialcarcinoma still may progress to invasive cancer. The recurrence of bladder tumors is not only relation withthe bladder tumor growth, multi-center surgical factors lead to tumor cell shedding planting and residualdisease, but also with multidrug resistance (multidrug resistance, MDR), and the MDR is one of theimportant factors in the failure of chemotherapy after TURB-t. NF-κB is an important nuclear transcriptionfactor onwards central transcriptional regulation of numerous genes, resulting in inflammation, immunity,cell proliferation, differentiation, apoptosis, degradation, tumor invasion and tumor resistance geneexpression. Some studies suggest that the nuclear transcription factor κB (NF-κB) involved in theregulation of tumor genes associated with multidrug resistance. Most anticancer drugs can activate NF-κBand its downstream gene. It may evade the killing effects of anticancer drugs to the tumor cells, resulting intumor resistance. Epirubicin(EPB）is one of the intravesical instillation chemotherapy drugs for bladdercancer after TURB-t, but its prevention and treatment of high-risk superficial bladder cancer recurrenceeffect is not very satisfactory. The reason may be related to EPB can induce NF-κB activation of tumorcells, leading to multidrug resistance. Eigallocatechin-3-gallate (EGCG) as the main active substance in thetea polyphenols has been shown to inhibit the activation of NF-κB of other tumor cells. We will observethe5637bladder cancer cell line growth inhibition situation and NF-κB activation and suppression of EPBcombined with EGCG, and to explore the mechanism in order to provide theoretical basis for furtherguidance on the clinical treatment for bladder cancer.Objective: To observe the inhibitory effect of EPB combined with EGCG on proliferation of high-risksuperficial bladder cancer cell (5637cell line) in vitro and elucidate its possible mechanism.Methods: With MTT assay to observe the inhibitory rate of5637cells after the treatment withdifferent concentrations of individual EPB, EGCG and EGCG plus EPB．With flow cytometer to detection the cell apoptosis rate. Among cell immunohistochemistry, Western blotting and CLSM to observe theexpression of nuclear factor-κB (NF-κB) in cytoplasms and nuclei．Results：(1) MTT assay results showed that with the increase of concentration of EPB and EGCG, the5637bladder cancer cell line growth inhibition rate was gradually increased. And when1μg/ml EPB combinedwith10μg/ml EGCG can significantly enhance the inhibitory effect of EPB on5637cell line．(2) Flow cytometer showed that both EPB(1μg/ml) and EGCG（10μg/ml）can induce apparentapoptosis of5637cell line, and the effect is better if they joint application．(3) Cell immunohistochemistry, Western blotting and CLSM demonstrated that most NF-κBtranslocated from cytoplasm into nuclei after EPB(1μg/ml) treatment．In contrast．the nuclear translocationof NF-κB in5637cell line was inhibited after combination treatment with EPB and EGCG．Conclusion：(1) EGCG combined with EPB can enhance the inhibition of5637bladder cancer cell lines, andwhen1μg/ml EPB combined with10μg/ml EGCG can significantly enhance the inhibitory effect of EPBon5637cell line．(2) The EGCG combined with EPB can effectively enhance the pro-apoptotic of the bladder cancer5637cell lines.(3)With the treatment of EPB, most NF-κB translocated from cytoplasm into nucleus, EGCG couldinhibit this migration phenomenon, this may be one of the mechanisms for enhanced efficacy. |
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