RAT INTESTINAL MEMBRANE--VITAMIN D-MEDIATED EFFECTS

描述：这项提案检查了维生素D和维生素D的能力 用于调节结肠癌细胞生长的衍生物。申请人及 他的同事们已经证明，F6-D3，一种氟化的，非钙化的类似物， 1-α，25(OH)2-D3降低结肠腺瘤发生率并预防 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 研究是在正常大鼠结肠和Caco-2细胞系中进行的 来源于人类结肠腺癌。这些细胞表现出类似的 信号转导机制和对维生素D的类似反应 和他们正常的对应者一样。此前的研究表明，维生素D 而F6-D3抑制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于G1期。 循环并导致细胞凋亡。因此，《公约》的具体目标 提案的目的是描述参与抑制的机制。 Caco-2细胞的增殖及类固醇的作用 在诱导细胞凋亡方面。

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.