PROSTAGLANDINS IN PROLIFERATION OF COLON CELLS

前列腺素在结肠细胞增殖中的作用

• 批准号: 2452860
• 负责人: T ELING
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2452860
• 关键词: antiinflammatory agents; apoptosis; arachidonate; butyrates; cell cycle; cell differentiation; colon neoplasms; drug screening /evaluation; eicosanoid metabolism; enzyme inhibitors; gene expression; growth factor; laboratory rat; neoplasm /cancer genetics; neoplastic transformation; phospholipase A2; prostaglandin endoperoxide synthase; prostaglandins; tissue /cell culture

The importance of arachidonic acid and linoleic acid metabolism is supported by animal and human epidemiology studies that indicate that aspirin and other NSAID drugs reduce the incidence and mortality of colon cancer. These drugs also induce regression of rectal polyps in patients with familial polyposis. Experimental studies with rodents indicate that NSAID reduce the both the size and number of colon tumors induced by carcinogens. Recent studies reported that PGHS-2 is significantly expressed in colon tumors compared to neighboring normal tissue. These data suggest that prostaglandins could play a major role in the development and progression of colon cancer. Our purpose to investigate the relationships between arachidonic acid metabolism and cell proliferation using a number of colon cell lines that are in several stages of differentiation and transformation. This project is in the early stages of development. We have obtained a number of colon cell lines that represent the various stages of genetic alterations that occur during the development of colon cancer. We are examining both arachidonic acid metabolism and the expression of PGHS-1 and-2 and cPLA2 in these cell lines. We will then measure the effect of NSAID drugs on growth factor induced (EGF,TGF) cell proliferation. Since some data suggest that prostaglandins can also alter apoptosis, we intend to determine if prostaglandins alter apoptosis in these cell lines. The effect of NSAID and prostaglandins could be due to either effects on cell proliferation or apoptosis. We observed in SW-480 cells that butyrate induced differentiation results in an increased expression of PGHS-1 and apoptosis. However, the addition of PGHS inhibitor did not alter the apoptosis in these cells. Further studies are planned using rat intestinal cell lines that high express PGHS-2 and are used as a model of colon cells. These studies will further define the potential use of NSAID as chemotherapeutic agents.

花生四烯酸和亚油酸代谢的重要性是 动物和人类流行病学研究表明， 阿司匹林和其他NSAID药物可降低结肠炎的发病率和死亡率 癌 这些药物还可诱导患者直肠息肉消退 家族性息肉病对啮齿动物的实验研究表明， NSAID可减少结肠癌的大小和数量， 致癌物质。最近的研究报道，PGHS-2是显着 与邻近的正常组织相比，在结肠肿瘤中表达。这些 数据表明，阿托兰丁可能在 结肠癌的发生和发展。我们调查的目的 花生四烯酸代谢与细胞的关系 使用在几种情况下的许多结肠细胞系进行增殖， 分化和转化阶段。 该项目正处于开发的早期阶段。我们已经获得了 结肠细胞系的数量，代表了遗传学的各个阶段， 在结肠癌的发展过程中发生的变化。我们 检测花生四烯酸代谢和PGHS-1的表达 and-2和cPLA 2的表达。 然后我们将测量 NSAID药物对生长因子诱导的（EGF，TGF）细胞增殖的影响。以来 一些数据表明，胡枝子素也可以改变细胞凋亡，我们打算 以确定前列腺素是否改变这些细胞系的细胞凋亡。的 非甾体类抗炎药和三尖杉酯碱的作用可能是由于对细胞的影响， 增殖或凋亡。 我们在SW-480细胞中观察到丁酸 诱导分化导致PGHS-1表达增加， 凋亡 然而，PGHS抑制剂的加入并没有改变 这些细胞的凋亡。 计划使用大鼠进行进一步研究。 高表达PGHS-2并用作模型的肠细胞系 结肠细胞。 这些研究将进一步确定 NSAID作为化疗剂。