| Summary: | 碩士 === 中國醫藥大學 === 營養學系碩士班 === 101 === Angiogenesis is invovled in the physiological processes including growth, development, wound healing, tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen, which is essential for endothelial cell survival, proliferation, and migration. Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, shows anti-carcinogenic potential both in vitro and in vivo. In this study, we investigated the molecular mechanism by which DHA down-regulates angiogenesis. We used HUVECs and fertilized chicken eggs as study models, and used chick chorioallantoic membrane (CAM) assay, MTT assay, Western blotting,wound healing assay, phosphatase activity assay and NO assay, to explore the anti-carcinogenic effect of DHA. The results showed that DHA, PD98059 (ERK inhibitor) and GW9508 (GPR120 agonist) inhibited VEGF-induced cell migration. Nevertheless, pretreatment with okadaic acid (OA, PP2A inhibitor) and S-Nitroso-N-acetyl-DL-penicillamine (SNAP, NO donor) reversed the cell migration inhibitory effect of DHA. VEGF induced angiogenesis was accompanied by phosphorylation of ERK and eNOS, as well as an increase in NO production. Treatment of HUVECs with DHA increased PP2A enzyme activity and decreased VEGF-induced phosphorylation of ERK and eNOS. However, pretreatment with OA significantly decreased DHA-induced PP2A enzyme activity and reversed the DHA inhibition of VEGF-induced ERK and eNOS phosphorylation. These results suggest that DHA abolishes VEGF-induced cell migratin via inhibition of VEGF-induced ERK/eNOS/NO signaling pathway and stimulation of PP2A activity. Taken together, anti-caricnogenic effect of DHA is at least in part by virture of its attenuation of cell migration which is essential for angiogenesis.
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