DEVELOPMENT OF CACO-2 CELLS EXPRESSING CYTOCHROME P450

我们建议评估表达人细胞色素的可行性 Caco-2人肠上皮细胞模型中的P450（P450）cDNA 用于研究药物/异生物质摄取和转运的系统。表达 研究将使用CYP 2A 6作为方便和适当的 模型酶，然后扩展到CYP 3A 4，主要的细胞色素P450， 人肠上皮细胞 转染的细胞对于 还将评估关于生物外源物质迁移的研究。总目标 是开发Caco-2细胞衍生物， P450在体内肠道中的发现，以建立一个更好的， 用于药物转运/代谢和用于检测 潜在治疗相关的药物-药物或药物-营养素 交互. 拟定的商业应用：一种改进的体外模型系统， 研究药物代谢和吸收。一个有用的系统，以帮助选择 应开发候选药物。

We propose to evaluate the feasibility of expressing human cytochrome P450 (CYP) cDNAs in Caco-2 human intestinal epithelial cells, a model system for the study of drug/xenobiotic uptake and transport. Expression studies will be conducted using CYP2A6 as a convenient and appropriate model enzyme and then extended to CYP3A4, the major cytochrome P450 in human intestinal epithelium. The suitability of transfected cells for studies of xenobiotic transport will also be evaluated. The overall goal is to develop Caco-2 cell derivatives which express the human cytochrome P450s found in the intestine in vivo in order to establish a better in vitro model system for drug transport / metabolism and for detecting the potential therapeutically relevant drug-drug or drug-nutrient interactions. PROPOSED COMMERCIAL APPLICATION: An improved in vitro model system to study drug metabolism and uptake. A useful system to help choose which drug candidates should be developed.