碩士 / 國防醫學院 / 生理學研究所 / 100 / Epidemiological studies have demonstrated that bladder cancer (BC) is the second most common urologic malignancy and accounts for approximately 90% of cancers of the urinary tract with a high mortality (50%) due to its high metastasis and recurrence rate. Otherwise, up to 50% patients with advanced cancer suffer from cachexia, resulting in weight loss and reducing survival time. Fucoidan, a sulfated polysaccharide purified from brown algae, possesses a variety of pharmacologic effects, including anti-inflammatory, anti-oxidant and anti-cancer properties. However, the molecular mechanisms of anti-cancer activity of fucoidan in human bladder cancer cells T24 are still unknown. It is known that ROS-activated Hypoxia-inducible factors (HIF-1α) during hypoxia, triggering vascular endothelial growth factor (VEGF) expression, plays an important role in tumor angiogenesis and progression. Our preliminary results showed that treatment with fucoidan dose-dependently inhibited hypoxia-induced ROS formation, HIF-1α translocation and nuclear protein accumulation. As expected, the remarkable elevation of VEGF protein expression and formation in T24 cells under hypoxic condition was dose-dependently inhibited by fucoidan. In addition, the anti-angiogenic effect of fucoidan in vivo by using a Matrigel plug assay.
In a xenograft mouse bladder tumor model, our data showed that treatment with fucoidan markedly reduced the tumor growth, angiogenesis and improved cancer and/or chemo drugs-induced cachexia accompanied by significant increase mice body weight compared with the control group. Together, these data suggest that fucoidan may inhibit human bladder cancer progression by suppressing HIF-1/VEGF-mediated angiogenesis, leading to improving cachexic symptoms and thereby provide a novel mechanism for the anticancer action of fucoidan.
| Identifer | oai:union.ndltd.org:TW/100NDMC0116006 |
| Date | January 2012 |
| Creators | Chi, Junghua, 戢蓉華 |
| Contributors | Chou, Tzchong, 周志中 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 83 |
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