EGCG Modulate the Cytotoxic Effects of Chemotherapeutic Agents in Human Urothelial Carcinoma Cells

(-)-epigallocatechin -3-gallate (EGCG) is the most abundant polyphenol compound from green tea, representing \~16.5% of the water-extractable fraction. EGCG have various bioactivities and can bind and regulate a wide range of molecular involved in cell cycle, signal transduction, and protein degradation. However, the anticancer effects of EGCG on UC have not been thoroughly explored. Our preliminary data show that EGCG alone can inhibit cell proliferation and induce apoptosis with the activation of caspases and PARP in a time dependent manner. Moreover, EGCG can enhance the cytotoxicity of several chemotherapeutic drugs in vitro. The underlying mechanism seems to be associated with Akt and ERK pathway. We will also check the Akt and ERK protein level by immunohistochemical staining in clinically chemoreistant bladder urothelial carcinoma specimens to further prove our in vitro findings. We will further confirm the effect of chemotherapeutic drugs combined with EGCG on UC in vivo via xenograft model. The specific aims of the study are: 1. To explore the anti-tumor effects of EGCG on human UC cells and elucidate the possible mechanisms. 2. To study the combinative cytotoxic effect of EGCG with other chemotherapeutic agents such as cisplatin, doxorubicin and gemcitabine on UC cells; moreover, to investigate the underlying mechanisms. 3. To investigate the expression level of phospho-Akt and phospho-ERK in clinically chemoreistant bladder urothelial carcinoma specimens to further confirm our finding in clinical events. . 4. To prove the in vitro findings and confirm the combinative efficacy of EGCG with chemotherapeutic agents in vivo by using the xenograft animal model. 5. To establish a novel therapeutic strategy for treatment of UC.