| Summary: | 碩士 === 中山醫學大學 === 生化暨生物科技研究所 === 102 === Osteosarcoma is a highly malignant bone tumor and is the most commonly encountered malignant bone tumor in children and adolescents. Osteosarcoma is about 20% in all bone tumor. Osteosarcoma patients often die owing to tumors metastasis to liver and lung. Flavonols(3-hydroxyflavone) is one of flavonoids, and flavonoids has been proposed as a potential drug for cancer chemoprevention and treatment because it is a natural polyphenol contained in plant-based foods. Recent studies have demonstrated that flavonoids protects against breast cancer and prostate cancer. Based on this finding, we investigated the mechanisms by which flavonols produces the anti-metastatic effect in human osteosarcoma cell U2OS. First, 3-hydroxyflavone significantly inhibited migration and invasion of U2OS cells based on results from the wound healing assay. The cytotoxic effect analysis indicated that 3-hydroxyflavone at the range of 0 to 50μM did not alter U2OS cells viability. 3-hydroxyflavone significantly also inhibited migration and invasion of U2OS cell in Boyden chamber invasion and migration assay. The protein levels of MMP-2 were decreased as shown by zymography assay. Then, the effect of 3-hydroxyflavone on cellular morphology-related proteins was slso examined by western blot, the 3-hydroxyflavone can inhibit p-FAK expression. To futher explore the detailed molecular mechanisms, we found the expression of phosph-Src、phospho-ERK1/2、and vimentin were suppressed by 3-hydroxyflavone through a western blot, it demonstrated that 3-hydroxyflavone could inhibit cell invasion、migration and EMT via Src、ERk1/2 pathway. These findings provide new insights into the molecular mechanisms involved in the anti-metastatic effect of 3-hydroxyflavone, and are valuable in the prevention of human osteosarcoma cell U2OS metastasis.
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