Elucidate the possible roles of chitosan in anti-tumorigenesis and its related pathways

• Main Authors: Fang-Hsiu Shen, 沈芳秀
• Other Authors: Ying-Jan Wang
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/03072515921857664646

碩士 === 國立成功大學 === 環境醫學研究所 === 91 === Chitosan derived from chitin by deacetylation in the presence of alkali present mainly in the exoskeleton of crustaceans. It has been reported that chitosan has various biological functions such as improving the symptom of fatty liver and hyperlipidaemia, enhancing the protecting effect of mice against bacteria infection, and avoiding metastasis of malignant cell. The present study was designed to investigate the anti-tumorigenic effects and related mechanisms of chitosan. LMWC (Low molecular weight chitosan) and HMWC (High molecular weight chitosan) were used to evaluate their anti-tumorigenic effects on gastro-intestinal cells, both in vivo and in vitro. We found that LMWC/HMWC possessed only limited G-I cancer cells inhibition effects both in cell culture and animal study. Thus, water soluble chitosan (WSC) was applied, instead of LMWC/HMWC, to test their anti-tumoeigenesis potency. Through a screening test of several cancer cell lines, the results showed that a significant inhibition effects was observed in AGS cells. Therefore, we further investigated the influence of cell cycle regulation of WSC on AGS cells. Flow cytometry analysis of cell cycle distribution indicated that the percentage of S phase reduced dramatically in cells treated with WSC. In addition, BrdU incorporation assay revealed a decreased DNA synthesis rate in treated AGS cells. Cell cycle-related genes expressions were analyzed and the results indicated that Cyclin D1, Cyclin D3, p21/Cip and p27/Kip were up-regulated, while the PCNA, BRBP and were down-regulated. Moreover, we also found that the activity of one of the metastasis-regulating proteins (MMP-2, MMP-9) could be inhibited in AGS cells treated with WSC. Base on the present findings, we concluded that WSC possess mild growth inhibition potency on AGS cancer cells. More studies are needed to further confirm the role of chitosan in cancer therapy or cancer chemoprevention.