| dc.description.abstract | Bladder cancer is one of the most frequent cancer of urinary tract and it’s nearly three time more common in men than women. The patients died of bladder cancer increase every year. It could be the effective treatments for tumors are not easy to achieve due to existence of metastases, tumor metastases mainly leads to high mortality rate of bladder cancer patients. In spite of advances in surgical techniques and improvements of systemic chemotherapies, there has been no change in the 5-year survival rate of bladder cancer. To overcome all these difficulties above, looking for a new drug is pressing need, which should be antitumor and anti-metastasis activities. In this research, quercetin-zinc (quercetin-Zn) was found that, it possessed not only potent anticancer activity, but was also able to effectively inhibit migration, invasion and metastasis of human bladder cancer cells (BFTC-905). Quercetin is one of the most bioactive flavonoids compound and present in many fruits, vegetables, beverages. Due to its anticancer, anti-oxidant and anti-inflammation activity, quercetin has been studied extensively as a chemoprevention agent in variety cancer models. However, quercetin was found to be difficult absorbed into the body, thus resulted in poor bioavailability. Interestingly, quercetin is the ideally compound for coordinate with metal to form a complex compound and enhance its biological activity with increasing bioavailability and also change the way deliver quercetin in vivo. The anticancer activity of quercetin-Zn complex has been demonstrated, therefore, quercetin-Zn is a promising complex in developing new medicine for cancer treatment. However, many aspects of the inhibitory effects of quercetin-Zn to tumor cells are not still completely understood. Quercetin is belong to extensive class of phenolic compounds, phenolic compounds have been report as a potential inhibitory effect on cancer invasion and metastasis, thus, it is believed that quercetin-Zn complex also own this property. In this work, quercetin-Zn was synthesized and its chemical properties were characterized by UV-VIS, FT-IR, 1H NMR, which showed that binding site via 3-OH and C4=O group. The anticancer effects of quercetin-Zn, quercetin and zinc ion on BFTC-905 and NHI-3T3 cells were compared. The result of cell viability on BFTC-905 cells demonstrated that killing effect was 2.8 time higher than quercetin alone. However, this effect was also found on NIH-3T3 cells, cytotoxic effect of quercetin-Zn on NIH-3T3 cells was shown to be higher than quercetin alone. In contrast, zinc ion was found to be non-toxic to both BFTC-905 and NIH-3T3 cells. Further investigation revealed the anti-metastasis effect of quercetin-Zn on BFTC-905 cells under non-cytotoxic concentration. In non-cytotoxic concentration range (0-50µM), BFTC-905 cells that were treated with quercetin-Zn significantly exhibited a concentration-dependent reduction in cell migration by wound healing assay. Based on the invasion assay result, after 24 h treatment with quercetin-Zn complex, the amount of BFTC-905 cells that invaded to the lower side of the membrane markedly reduced compare with control (p-value<0.05), suggested that BFTC-905 cells were treated with quercetin-Zn complex display significant reduction in invasive capacity. Furthermore, in order to investigate the anti-metastasis mechanism of quercetin-Zn complex, the expression of AKT and MT1-MMP were examined. We found that, the expression of p-AKT and MT1-MMP level were down-regulated in quercetin-Zn-treated BFTC-905 cells. Importantly, these findings provide better understanding for the molecular pathway of quercetin-Zn complex on suppression of migration and invasion which might be useful as a therapeutic strategy to treat human bladder cancer. | en_US |