MRP/GST SYNERGY IN MULTIDRUG RESISTANCE

MRP/GST 在多重耐药性方面的协同作用

• 批准号: 6688931
• 负责人: CHARLES S MORROW
• 金额: $ 24.48万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-10 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6688931
• 关键词: antineoplastics; antitoxins; cell free system; chemical conjugate; cytotoxicity; detoxification; drug interactions; drug metabolism; drug screening /evaluation; enzyme activity; enzyme substrate; gene expression; glucuronides; glutathione; glutathione transferase; isozymes; melphalan; membrane transport proteins; mitoxantrone; multidrug resistance; neoplasm /cancer pharmacology; pharmacokinetics; tissue /cell culture; transfection

The mechanisms involved in detoxification of drugs and poisons are important to cancer biology. The ability of a cell or tissue to detoxify xenobiotic poisons are associated with the emergence of anti-cancer drug resistance in tumors. In normal tissues, this detoxification activity influences the outcome of exposure to carcinogens and other toxins. A long term goal of the studies proposed is to understand the mechanisms by which the drug conjugating system, glutathione (GSH) and glutathione transferase (GST) and glutathione transferase (GST), and the toxin efflux transporters, MRP1 and MRP2, operate together to confer protection from anti-cancer drugs or carcinogens. This knowledge will improve the ability to predict the responses of particular tissues and tumors to toxin exposure including the risk of developing cancer in normal tissues or the likelihood of develop drug resistance in cancer. Moreover, this knowledge can be used to device more effect ant-cancer treatment or chemopreventive strategies.

药物和毒物的解毒机制对癌症生物学很重要。细胞或组织解毒异生物质毒物的能力与肿瘤中抗癌药物耐药性的出现有关。在正常组织中，这种解毒活性影响暴露于致癌物和其他毒素的结果。提出的研究的一个长期目标是了解药物缀合系统谷胱甘肽（GSH）和谷胱甘肽转移酶（GST）和谷胱甘肽转移酶（GST）以及毒素外排转运蛋白MRP 1和MRP 2共同发挥保护作用以免受抗癌药物或致癌物侵害的机制。这些知识将提高预测特定组织和肿瘤对毒素暴露的反应的能力，包括正常组织中发生癌症的风险或癌症中发生耐药性的可能性。此外，这些知识可以用于设计更有效的抗癌治疗或化学预防策略。