| Endothelial cell (EC) proliferation, migration and tubules formed by EC in tissue are the crucial processes in tumor angiogenesis. Anti-angiogenesis has been accepted as a new therapeutics for cancers. Malignant gliomas are highlyvascularized and active endothelial cell proliferation of the microvessels is reported to be the marker of high malignancy and poor prognosis. Therefore, investigation on microvessels in malignant glioma will be important to a better understanding of the mechanism of tumor angiogenesis. Nordihydroguaiaretic acid (NDGA), a specific inhibitor of lipoxygenases, is a natural compound existing in Larrea divaricata and Guaiacum offrcinale. It has been found that NDGA has multiple biological activities including its anti-cancer effect, which may constitute a basis for the development of anti-cancer agents. Based on the chemical structure of NDGA, we synthesized it and produced the anti-tumor compound Nordy. Our studies in vitro and in vivo showed that it could not only inhibit the growth of tumor cells but also induce tumor cell differentiation. More recently, we found it could inhibit tumor growth and neovascularization in transplanted tumors of human glioma in nude mice. The detailed mechanism of this effect needs better explanation. The present study focused on the inhibitory effect of Nordy on in vitro angiogenesis by endothelial cells in a 3D angiogenesis model. The main results and conclusions are as follows:1. Using collagen as extracellular matrix and malignant glioma cells as producer of proangiogenic factors, a 3D model of endothelial tubule-like structure formation was established and its features were studiedEndothelial cell line ECV304 cells were cultured in the medium containing collagen from rat tails and the cells were induced by the supernatant from malignant glioma cells (SHG-44) to form endothelial tubule-like structure, which could be used as a 3D model for in... |
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