【作者】 陈俊；

【导师】 庄东红； 李恩民； 许丽艳；

【作者基本信息】 汕头大学 ， 生物化学与分子生物学， 2008， 硕士

【摘要】 为了从植物材料中筛选有抗癌活性的物质,我们选择了肿瘤中普遍高表达的脂肪酸合酶(FAS)为靶标。本研究应用分光光度法检测了11种肿瘤细胞包括食管癌胃癌、肺癌、肝癌和白血病等细胞中的FAS的活性,从中选择FAS活性高的细胞株,作为筛选脂肪酸合酶抑制剂的模式细胞来。实验选取了广东东部常见的四种植物材料:橄榄(Canarium album)叶、木棉(Bombax malabarica)花、芥蓝(Brassica alboglabra )和潮州柑(Citrus poonensis)果皮,进行植物总黄酮的提取,并用植物总黄酮提取物对模型细胞中FAS进行抑制实验。我们根据FAS抑制实验检结果选择对FAS抑制效果最好的两种植物总黄酮提取物作用于培养的食管癌细胞用于检测它们对细胞增殖的影响。同时我们的研究针对潮汕地区高发的食管癌疾病,选取了48例临床食管癌组织标本,探究食管癌组织和对应的癌旁正常食管组织中FAS活性的差异。实验结果显示各种肿瘤细胞的FAS活性存在明显差异,以胃癌细胞N87为最低,仅为15.91±3.61U/mg蛋白,而肺癌细胞A549活性最高,达到127.36±10.14U/mg蛋白。因此本实验以A549为模型细胞。FAS抑制实验的结果显示潮州柑果皮总黄酮提取物和橄榄叶总黄酮提取物对脂肪酸合酶的抑制效果明显优于通用的FAS抑制剂C75。用筛选到的植物总黄酮提取物作用于食管癌细胞H5E973,发现它们明显地抑制了细胞的增殖。但不像通用的FAS抑制剂C75和黄酮纯品Morin那样引起细胞形态的变化。临床食管癌样本中FAS的活性情况的统计结果显示FAS的活性在食管癌组织和正常食管组织中的差异不显著。这提示我们在食管癌中,癌细胞可能是通过FAS量的改变而不是FAS活性的改变来适应细胞对脂质的需求。更多还原

【Abstract】 For the purpose of finding anticancer bioactive components from plant materials, we select the over-expressed enzyme in cancer tissues, fatty acid synthase (FAS), as our target. we compared FAS activity in 11 different cancer cells, include esophageal cancer cells, gastric cancer cells, lung cancer cells, liver cancer cells and leukemia cells, with spectrophotometric method and selected the highest FAS activity cancer cell line as our cell model.We selected four common plant in east of Guangdong, including Canarium album leaves, Bombax malabaricum, Brassica alboglabra and Citrus reticulate, to extract flavonoids. The inhibitory effect of total flavonoids extracts from selected plants on FAS from model cell had been determined and two plant flavonoids extracts with superior inhibitory effects were used for the test on cultured esophageal cancer cells. Correspondingly, we had drawn 48 esophageal carcinoma (high-occurring disease in Chaoshan region) clinical samples and compared the FAS activity between cancer and normal tissues.The results showed FAS activity were different between different cancer cells. The FAS activity is lowest in gastric cancer cells N87(15.91±3.61U/mg) and highest in lung cancer cells A549(127.36±10.14U/mg).So we choose A549 as model cell. Results of FAS inhibitory test showed that the total flavonoids extract of Citrus poonensis and Canarium album leaves are better FAS inhibitor compared with the universal used FAS inhibitor C75. The test of plant flavonoids extracts on cultured esophageal cancer cells H5E973 show that both of them inhibit the proliferation of cancer cells without influence cell morphous while FAS inhibitor C75 and flavonoid Morin do. The statistic analysis results of FAS activity in esophageal carcinoma clinical samples show that FAS activity has no significant difference between FAS in normal and cancer tissues. It implied esophageal carcinoma cells may not through changing FAS activity but FAS quantity to supply it’s need for fatty acid.更多还原