RAT INTESTINAL MEMBRANE--VITAMIN D-MEDIATED EFFECTS

大鼠肠膜——维生素 D 介导的作用

• 批准号: 6177020
• 负责人: MICHAEL D SITRIN
• 金额: $ 28.05万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6177020
• 关键词: 1,25 dihydroxycholecalciferol; adenocarcinoma; antineoplastics; antisense nucleic acid; apoptosis; cancer prevention; cell growth regulation; ceramides; chemoprevention; colon neoplasms; cyclins; drug screening /evaluation; enzyme activity; fluoride ion; gastrointestinal pharmacology; gene induction /repression; guanine nucleotide binding protein; intestines; laboratory rat; neoplasm /cancer pharmacology; nutrition related tag; protein kinase C; tissue /cell culture; transfection; tumor suppressor proteins

DESCRIPTION: This proposal examines the ability of vitamin-D and its derivatives to regulate cell growth in colonic cancer. The applicant and his coworkers have shown that F6-D3, a fluorinated, non-calcemic analog of 1-alpha,25 (OH)2-D3 reduced the incidence of colonic adenomas and prevented the development of adenocarcinomas in experimental models. In order to understand the role of vitamin D3 in colonic normal and abnormal function, studies are proposed in normal rat colon and in CaCo-2 cells, a cell line derived from a human colonic adenocarcinoma. The cells exhibit similar signal transduction mechanisms and respond in similar fashion to vitamin D as their normal counterparts. Previous studies have shown that vitamin D and F6-D3 decreased cellular proliferation in these cells, while more recent studies have shown that they induce growth arrest in the G1 phase of cell cycle and bring about apoptosis. Accordingly the specific aims of the proposal are to characterize the mechanisms involved in inhibition of cellular proliferation in CaCo-2 cells and the actions of the secosteroids in inducing apoptosis.

描述：本提案考察了维生素D及其 用于调节结肠癌细胞生长的衍生物。 申请人和 他的同事已经证明，F6-D3，一种氟化的，非钙离子类似物， 1-α，25（OH）2-D3降低结肠腺瘤的发病率， 腺癌在实验模型中的发展。 为了 了解维生素D3在结肠正常和异常功能中的作用， 提出了在正常大鼠结肠和CaCo-2细胞中的研究， 来源于人结肠腺癌。 细胞表现出类似的 信号转导机制和维生素D类似的方式作出反应 和正常人一样 此前的研究表明，维生素D 和F6-D3降低了这些细胞的细胞增殖，而最近 研究表明，它们诱导细胞生长停滞在G1期， 循环并导致细胞凋亡。 因此， 建议是表征参与抑制的机制， CaCo-2细胞增殖及开环甾体类化合物的作用 诱导细胞凋亡。