| The tumor angiogenesis plays an important role in the growth and metastasis of the tumor. In the 70s of the 20th century, Folkman first discovered that the proliferation and metastasis of the solid tumor depends on the genesis of the newly-born blood vessels, and is regulated by the angiogenesis stimulating factor and inhibitive factors. He then postulated that the tumor growth could be inhibited by inhibiting angiogenesis, and established the theory and practice of the cure of the tumor through the anti-angiogenesis. The tumor angiogenesis is mainly affected by the two factors: the growth and proliferation of the vascular endothelial cell (EC) of the tumor and the relevant factors expression which facilitate angiogenesis formed by the tumor tissue cells and by the vascular endothelial cell. The relevant factors expression of breast cancer which facilitate angiogenesis are vascular endothelial growth factor (VEGF), urokinase type plasminogen activator (uPA), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). These factors are able to facilitate endothelium cells growth and proliferation, destroy the barrier of the tissues formed by the basement membrane and extracellular matrix and hence allow the metastasis of the vascular endothelial cell. There are studies showing that there is a positive relationship between the expressions of the MMP-2, MMP-9, uPA, VEGF and the microvessel density (MVD) in the breast cancer tissues, and hinting that MMP-2, MMP-9, uPA and VEGF are probably the important factors which influence the angiogenesis of breast cancer.The ability of angiogenesis of the HER-2/neu overexpressing breast cancer which posseses protein tyrosine kinase (PTK) property is strong and the degree of cancer malignancy is high. There are studies showing that the expressions of the MMP-2, MMP-9 and uPA of breast cancer depends on the PTK signal transduction pathway, and inhibiting the PTK activity may lower the expressions of the MMP-9 and uPA. The HER-2/neu antibody against the HER-2/neu overexpressing breast cancer cells may cause the reduction of the VEGF with dose-dependence. There may a close relationship between the expressions of MMP-2, MMP-9, uPA, VEGF and PTK activity of the breast cancer cells.Genistein is an important non-nutritious element of soy and has the function of curing cancer. There are studies showing some mechanisms of the cancer prevention by genistein: antiestrogen, inhibiting the proliferation of the tumor cells, improving the ability of immunity and inducing the apoptosis of tumor cells. There are other studies showing that genistein is able to inhibit angiogenesis so as to inhibit the growth of bladder and prostate cancers. Genistein is a naturally strong and highly efficient inhibitor of PTK activity. So we hypotheses that genistein, on the one hand, may inhibit the expressions of the MMP-2, MMP-9, uPA and VEGF of the breast cancer cells by regulating the PTK activity of HER-2/neu receptor, and on the other hand, may inhibit the PTK activity of growth factor receptor of the vascular endothelial cell, lower the mitogen-activated protein kinase (MAPK) activity. Genistein may inhibit the angiogenesis of the HER-2/neu overexpressing breast cancer through the two ways. However, few researches report that genistein inhibit angiogenesis of HER-2/neu overexpressing breast cancer and we are not clear of its mechanism and need to make further research.Based on the above analysis, combining the progress of the research both at home and abroad, this study, first in vivo adopt the nude mouse animal model of HER-2/neu overexpressing breast cancer cells xenograft tumor to observe the influence of genistein on the angiogenesis of the xenograft tumor, and then in vitro adopt the MDA-MB-453 cells (ER-) and the MCF-7/HER2 breast cancer cells (ER+), which also are HER-2/neu overexpression, to research the relationship between the influence of genistein on the angiogenesis of HER-2/neu overexpressing breast cancer and the expressions of MMP-2, MMP-9, uPA , VEGF and it...
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