| Summary: | 碩士 === 國立成功大學 === 環境醫學研究所 === 92 === Chitosan oligosaccharides are widely present in the exoskeleton of crustaceans and in cell walls of fungi, insects and yeast. There are nontoxic oligomers derived from chitin and chitosan by either chemical or enzymatic hydrolysis. Previous studies indicated that chitosan oligosaccharides have ability to lower hyperlipidaemia, antioxidant, immuno-enhancing effects, antifungal and anti-tumor activity, making it becoming a popular healthful food in the past few years. So far, the mechanisms of anti-tumor growth and anti-metastasis of malignant cells by chitosan oligosaccharides are unclear and needed further investigation. In the present works, the in vitro and in vivo studies were designed to evaluate the anti-cancer potency and related pathways of chitosan oligosaccharides. In in vitro studies, we found that chitosan oligosaccharides significantly inhibited human hepatocellular carcinoma (HepG2 cells) proliferation by using MTT assay. Flow cytometry analysis of cell cycle distribution indicated that the percentage of S phase reduced in cells treated with chitosan oligosaccharides. In addition, BrdU incorporation assay revealed a decreased DNA synthesis rate in chitosan-treated HepG2 cells. Cell cycle-related gene expression were analyzed by western blot and the results indicated that cyclin D3, p21 and p27 were up-regulated, while the cyclin A, cyclin B and cdk-2 were down-regulated. Moreover, we also found that the activity of one of metastasis related proteins (MMP-9) could be inhibited in LLC cells . In in vivo studies, we also found that chitosan oligosaccharides inhibited the growth of HepG2 xenografts in SCID mice. In LLC-bearing mice tumor growth and lung metastasis model, tumor volume in early stage and lung colonies could be inhibited by chitosan oligosaccharides. Our results suggest a potential anti-cancer potency of chitosan oligosaccharides in caner chemoprevention.
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