| Summary: | 碩士 === 臺灣大學 === 藥理學研究所 === 98 === Angiogenesis, forming new capillaries from the pre-existing blood vessels, is essential for many physiologic processes as well as many pathological disorders. Endothelial cells play an important role in the processes of angiogenesis including cell proliferation, migration, differentiation and tube formation. Anti-angiogenic agents reduce the tumor vasculature and growth, thereby being a therapeutic strategy for cancer. In this study, we screened a series of compounds by MTT assay to investigate the action on human umbilical vein endothelial cells (HUVECs). Among these compounds, Than42 exerts a more potent effect, therefore we further explore the mechanism of Than42 on HUVECs and angiogenesis.
We found Than42 inhibited HUVEC proliferation by BrdU proliferation assay. Furthermore, we found Than42 inhibited cell proliferation by inducing cell apoptosis as evidenced by the increased sub-G1 phase using flow cytometry. In addition, Than42 inhibited VEGF-induced cell migration and tube formation in vitro in a concentration-dependent manner. Moreover, Than42 also inhibited endothelial cells sprouting from aortic ring stimulated by VEGF. We also found Than42 inhibited VEGF-induced angiogenesis in Matrigel plug assay in vivo. Besides, Than42 blocked the activation of PI3K-Akt pathway and ERK1/2 stimulated by VEGF treatment. In conclusion, Than42 exhibits anti-angiogenic activity both in vitro and in vivo by inducing endothelial cell apoptosis and inhibiting cell migration, tube formation, and signaling induced by VEGF. These results suggest that Than42 has a potential to be a candidate for drug development in field of anti-angiogenesis.
|
|---|
