肿瘤细胞中药物代谢酶表达和活性的研究与进展.pdf

瘤细胞中药物代谢酶表达和活性的研究与进展 肖文璟，王广基，阿基业* （中国药科大学药物代谢动力学重点实验室，南京，江苏，210009 ） 摘要：肿瘤细胞具有十分独特的生存与代谢模式，研究肿瘤细胞的药物代谢特征对于了解药物 在肿瘤细胞中的代谢和消除快慢进而评估并预测药效、基于代谢特征优化抗肿瘤药物/前体药 物设计具有重要意义。本文综述了肝、肠、乳腺和肺等常见癌组织的主 药物代谢相关酶的表 达/活性及其与正常组织的差异，阐述了部分典型抗肿瘤药物在肿瘤组织中的代谢特征，结合 对应的常用体外培养肿瘤细胞株中药物代谢酶的表达/活性特征，探讨实体肿瘤组织 （体内） 和肿瘤细胞株 （体外）中酶表达与功能的异同性及差异的产生原因。 关键词：肿瘤组织/细胞；体外培养细胞株；药物代谢酶；药物设计 中图分类号：R963 A review of the expression and activity of drug metabolism enzymes in tumorous cells XIAO Wen-ji ng, WANG Guang-ji , AA Ji-ye* (Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanji ng, Jiangsu, 210009, China) Abstract: Tumorous cells are characterized by distinctive metabolic reprogramming and living conditions. Understanding drug metabolizing features in tumor cells will not only favor the estimation of metabolic rate, elimination half life and the assessment of potency, but also facilitate the optimal design of anti-tumor drugs/prodrugs. This article reviews the expression and activity features of maj or drug metabolizing enzymes (DMEs) in solid tumorous tissues, such as liver, 收稿日期：2014-03-14；修回日期：2014-04-14. 基金项目: 江苏省自然科学基金资助项目(BK2012762). *通讯作者 Tel: 86-25-8327-1176, Fax: 86-25-8327-1060, E-mail: j iyea@cpu.edu.cn. 2 intestine, breast and lung, and the difference from the correspondingly normal tissues, exemplified by the metabolic properties of some classic antitumor-agents in tumorous tissues. In combination with the data retrieved in vitro tumor cell lines, we discussed the similarities and differences of DMEs expression and function between tumor tissues (in vivo) and tumor cells (in vitro), and proposed the possible factors that cause the differences. Keyword: tumor tissues/ cells; in vitro cell lines; drug metabolizing enzymes; drug design 1