The studies on the inhibitor of tumor angiogenesis

• Main Authors: Ja-Wen Young, 楊介文
• Other Authors: Rong-Tsun Wu
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/13941183468041139959

碩士 === 國立陽明大學 === 生物藥學研究所 === 91 === Abstract: Currently strategies of cancer therapy are based on chemotherapy. Because of the cytotoxicity on normal cells, there is a bottleneck in the development of traditional cancer therapy. Folkman J. proposed anti-tumor angiogenesis at 1971, and the new concept offer novel strategies of cancer therapy. Thalidomide originally developed as an anti-morning sickness drug, but had been terminated clinically used because of its teratogenic effect. Thalidomide has been previously shown to inhibit angiogenesis induced by basic fibroblast growth factor in vivo at 1994. Thalidomide also has activity in patients with multiple myeloid, recurrent high-grade gliomas and metastatic prostate cancer. But until now, the mechanism of thalidomide in anti-angiogenesis and teratology is still unknown. We established mice Lewis lung carcinoma (LL-2), endothelial progenitor cells (EPC) co-culture system to mimic tumor induced vasculogenesis. While, we established human hepatoma (Huh-7), human umbilical vascular endothelial cells (HUVEC) co-culture system to mimic tumor induced angiogenesis. Further, we tried to validate possible mechanism of thalidomide by using these systems. Bone marrow EPC is considered to play an important role in cancer induced vasculogenesis. We found that thalidomide significantly inhibit the differentiation of EPC induced by cancer cells at the concentration of 0.1 μg/ml. Thalidomide doesn’t have distinct inhibitory effect on growth of non-co cultured HUVEC, EPC and cancer cells. But, thalidomide inhibits the growth of HUVEC, Huh7 and LL-2 in our co-culture system. We also found thalidomide can inhibits the expression of bFGF, VEGF, c-myc in EPC, HUVEC, LL-2, and Huh7 using RT-PCR. Moreover thalidomide inhibits bFGF protein expression on HUVECs and Huh7. Thalidomide strongly inhibits HMW bFGF expression on Huh7. These results indicate that the differentiation of EPC might be the primary effects of thalidomide and bFGF may play an important role on this inhibitory effect. Base on previous study, we tried to test if thalidomide inhibits bFGF expression by interacting with the bFGF GC-rich coding region. We found the chemical shift of thalidomide was changed with adding the bFGF GC-rich coding region by NMR. These data suggested that thalidomide might interact with bFGF GC-rich coding region.