| Summary: | 碩士 === 國立陽明大學 === 藥理學研究所 === 90 === Angiogenesis, the formation of new blood vessels, has an essential role in malignant tumor development. Inhibition of tumor angiogenesis is a therapeutic strategy that can inhibit tumor growth and metastases. In this study, the antitumor growth and antiangiogenic activity of genistein, a natural isoflavonoid compound found in soy products were investigated. In vitro experiments showed that genistein inhibited human umbilical vein endothelial cells (HUVEC) proliferation and migration. The results from tube formation of HUVECs on matrigel confirmed that genistein suppressed angiogenesis. Furthermore, the activity of genistein in inhibiting angiogenesis induced by tumor cells was examined. It was observed that the proliferation and tube formation of HUVECs were enhanced by conditioned medium of gastric cancer cells (SC-M1), and this enhancement of proliferation and tube formation was abrogated by genistein. These effects of genistein were found to be mediated by reducing the protein level of vascular endothelial growth factor (VEGF), a potent angiogenic factor. Using flow cytometric analysis, it was found that genistein slightly decreased VEGFR-2 expression on HUVECs and the expression of VEGFR-2 was also detected on SC-M1 cells. Low cytotoxicity of genistein to both HUVEC and SC-M1 cells was also shown by propidium iodide exclusion assay. In addition, flow cytometric analyses revealed that genistein induce G2/M arrest in SC-M1 cells. Taken together, these results suggest that genistein may inhibit the growth of SC-M1 cells and tumor-induced angiogenesis in vitro by regulating VEGF expression in gastric cancer cells.
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