Studies on the Inhibitor of Tumor Angiogenesis

• Main Authors: Szu-Chieh Mei, 梅思潔
• Other Authors: Rong-Tsun Wu
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/su525s

博士 === 國立陽明大學 === 生物藥學研究所 === 96 === Thalidomide is an old drug with a wide variety of molecular mechanisms. Many clinical data showed that thalidomide has anti-angiogenic activity and the responder showed a significant decrease of serum bFGF level after treatment. Since bFGF is an important factor for regulating limb development, the teratogenic activity of thalidomide may also be accounted by its decrease of bFGF level. In this study, by using low dose treatment, we found that thalidomide can diminish bFGF level in cell. Thalidomide suppressed the transcription and translation of bFGF gene through directly interacting with the GC rich regions located in its promoter and IRES region of its transcripts, respectively. Although this drug failed to suppress the two-dimensional growth of glioma cells, it significantly inhibited characteristics of tumor of glioma cells. Using RNAi to knock-down cellular bFGF levels in U-87 MG cells, we confirmed that bFGF is important for the tumorigenicity of glioma cells and the anti-tumor activity of thalidomide may due its effect on down-regulating bFGF expression. Thalidomide was found to have anti-angiogenic activity, but the doses used in previous studies were too high. Despite thalidomide had only minor activity on endothelial cells when cultured alone, it can strongly down-regulate tumor induced angiogenesis in a dose-dependent manner. Beside endothelial cells, we also study the effect of thalidomide on vasculogenesis and found that thalidomide could inhibit tumor induced differentiation of endothelial progenitor cells which could be an interest target for further study. In conclusion, I showed that thalidomide can inhibit glioma growth and has anti-angiogenic activity at low concentration. The data may have important implications for understanding the mechanistic rationale for thalidomide use in the clinical realm of cancer therapy.