Summary: | 博士 === 中山醫學大學 === 生化微生物免疫研究所 === 104 === Bladder cancer is the second predilection urinary system cancer, cancer is currently Taiwan''s top ten ranked seventh. The treatment of bladder cancer by cystectomy combined with the treatment of chemotherapy and radiation because of the prevention of cancer is not clean. But whether chemicals or radiation will cause the patient in the physical side effects, in addition to the cancer cells also easy to become resistant to chemotherapy or radiation, or allergy, leading to treatment failure. In order to solve the blind spot for the treatment of bladder cancer, and is now actively adding natural herbs or food as a sensitizer in the treatment, helping to reduce the dose of poison clinical stage cancer patients to help reduce the physiological Side effects and drug resistance, or even prevent recurrence and metastasis. Our studies found that Mulberry water extract (MWE: 250-1500 ug/ml) combined with paclitaxel (dose: 3 nM) or radiation (dose: 10 Gy) for bladder cancer cells line (TSGH 8301) than the use of drugs alone have a better cytotoxic effect, and further found that MWE combined with paclitaxel (MWE/paclitaxel) or IR (MWE/IR) will result cycle arrest in G2/M phase in 48 hours in TSGH 8301 cells line, and promotes mitotic catastrophe -related proteins, such as Aur- A, Plk1, Rho A and Cep55 expression. MWE/paclitaxel decreased the immunofluorescence stain of early endosome antigen 1 (EEA1) and increased the expression and phosphorylation of phosphatase and tensin homolog (PTEN) indicating that the regimen inhibited the formation of recycling endosome which is required for cytokinesis. MWE/IR decreased phospho-Aur- B expression via Ras/Raf/MEK/ERK/MAP kinase pathway to inhibit cytokinesis. We found further that two combined treatments induced apoptosis of cancer cells and caused cell death after 72 hours finally. In a TSGH 8301 xenograft model, MWE/Paclitaxel retarded tumor growth via activation of PTEN and Caspase 3 and MWE/IR via inhibited Aur- B. These data demonstrated a synergistic effect on the anticancer efficacy of paclitaxel or IR by MWE supplement via promoting mitotic catastrophe through activation of PTEN and inhibition of Aur- B, and provide a novel and effective therapeutic option for bladder cancer treatment strategies.
|