Effects Of Myricetin On The Apoptosis Of Bladder Cancer Cell BIU-87

Bladder cancer is one of the most common genitourinary cancer, and its incidence is adscendent tendency in the lately years. About two-thirds of bladder cancer is superficial bladder cancer. The bladder cancer has the clinical characteristics of high postoperative recurrence rate. 70% of superficial bladder cancer is to be recurrence within 5 years, and the degree of malignancy will increase in 20% to 30% of superficial cancer. Therefore, a regular intravesical infusion therapy with antineoplastic drugs has a very important clinical significance to prevent postoperative recurrence of superficial bladder cancer. A desirable antineoplastic drug must possess the advantage of efficacy, less toxic side effects and less adverse effect, as well as they can rapidly achieve effective concentration in the bladder epithelial cells to kill the residual tumor cell. But, now antineoplastic drugs that are used in the intravesical infusion therapy have the characteristic of comparatively strong systemic toxicity, local irritation and low efficiency. So, it is an urgent practical problem to search for a new neoadjuvant drug so as to decrease postoperative recurrence rate of bladder cancer. Several researches showed that natural phytochemical drug have antineoplastic properties and relative nontoxic. Myricetin is a kind of natural flavonoids. It has some pharmacological actions, such as antioxygenation, hypoglycemic activity, platelet-activating factor (PAF) antagonist activity, bacteriostasis, protecting effect of liver and reducing neurotoxicity. One of the main pharmacological actions is antitumor effect, which has been demonstrated by some experiment, and the detailed mechanism has become the focus of research recently. The study was designed to observe the effect of myricetin on the proliferation of bladder cancer cell lines BIU-87, and discussed the effects and mechanism of myricetin on bladder cancer cell lines in order to provide theoretical basis and methods for the prevention of postoperative recurrence of bladder cancer.Objective: To investigate the effect of myricetin on the proliferation and apoptosis of bladder cancer BIU-87 cell, and to explore its potential action mechanism.Methods: BIU-87 cell was cultured, and different concentration of myricetin was added into the culture. The cell morphology was observed under reverse microscope, meanwhile the concentration of myricetin was determined by MTT assay and the optimization drug concentration were choose for fellow-up research. Using Hoechst 33258 staining, the effect of myricetin on the apoptosis of bladder cancer BIU-87 cell was tested. RT-PCR was performed to detect expression level of apoptosis associated genes survivin and caspase-3 and western blot was performed for analysis of the expression level of survivin and caspase-3 protein.Results: The result of MTT showed that myricetin inhibited the proliferation of BIU-87 cell and the effect was in a time- and dose-dependent manner. The cell growth inhibition rate was 50% when the concentration of myricetin was 40μg/ml. We observed that apoptotic rates gradually enhanced followed by the concentrations increasing using Hoechst 33258 staining, and RT-PCR and western blot showed that the transcription and expression of survivin and caspase-3 correlated with the concentration of myricetin. The result was the down-regulated expression of survivin and up-regulated expression of caspase-3.Conclusions: Myricetin could markedly induce apoptosis of bladder cancer BIU-87 cell, and its mechanisms may be associated with down-regulation of survivin expression and up-regulation of the expression of caspase-3. This provides proper theory foundation for myricetin to be used in clinic and searching new methods for the treatment in the patients with bladder cancer.