| Summary: | 碩士 === 國立嘉義大學 === 生物醫藥科學研究所 === 98 === Bladder cancer is the most common urological cancer in Taiwan, and approximately 90% of bladder cancers are transitional cell carcinoma (TCC). Metastasis, a major cause of death from cancer, can be divided into the following steps: cell dissociation, invasion, intravasation, distribution to distant organs, adhesion to endothelial cells, extravasation, invasion into the target organ and proliferation. Because metastasis accounts for about 90% of cancer death, searching new anti-metastasis drugs is very important for late-phase disease control. In this study, the anti-metastasis effect of two antioxidants, curcumin and baicalein, was analyzed by a series of in vitro and in vivo assays. In in vitro assay, we found that curcumin and baicalein have a dose-dependent cytotoxicty in human bladder cancer cells 5637 and mouse bladder cancer cells MB49. The effect of these two phytochemicals on soft agar anchorage-independent growth assay, a best mimic assay for tumorigenicity in animals, was analyzed in MB49 cells. It shows that curcumin and baicalein dose-dependently reduced the colony formation. The in vivo anti-metastasis assay was evaluated by an experimental pulmonary metastasis animal model. It shows that bladder cancer cell lung metastasis was reduced in about 50% of mice by curcumin and 70% by baicalein. The incompletely inhibition phenomenon suggests that there might be some individual differences between mice. Therefore, we analyzed the activities of antioxidant enzyme catalase and found that the catalase activities correlated with anti-metastasis effect. The immunohistochemistry of lung tissue containing metastatic tumors was also analyzed by anti-heme oxygenase-1, anti-superoxidase-2, and found that there was no correlation between tumor number and superoxidase-2 expression. It also shoes no correlation between tumor number and heme oxygenase-1 expression. Collectively, these data demonstrate that curcumin and baicalein have anti-metastasis effects in mice, and this effect might correlate with the activities of endogenous antioxidant enzyme catalase.
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