ALTERATIONS IN ANTICANCER DRUG ACTIVITY BY ANGUIDINE

安奎定抗癌药物活性的改变

• 批准号: 3734539
• 负责人: CLIFTON ORR
• 金额: --
• 依托单位: UNIVERSITY OF ARKANSAS AT PINE BLUFF
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3734539
• 关键词: antineoplastics; bleomycin; cell growth regulation; cis platinum compound; clone cells; colorimetry; dosage; doxorubicin; drug adverse effect; drug interactions; drug receptors; inhibitor /antagonist; neoplasm /cancer pharmacology; protein biosynthesis; urinary tract neoplasms

Anguidine, a protein synthesis inhibitor, is the principle phytotoxic metabolite of the plant parasitic fungus Fusarum equiseti. Anguidine can preferentially induce a reversible cell cycle arrest in normal versus tumor cells. Such selective cell cycle arrest afforded preferential protection of the normal cells against the cytotoxicity of antineoplastic agents with S-phase activity like Adriamycin and 1-B-D-arabinofuranosyl- cytosine. In contrast to its protective effects with S-phase agents, anguidine can potentiate the cytotoxicity of DNA-reactive antineoplastic agents like cis-platinum, melphalan, and bleomycin. In view of the broad application of the DNA-reactive antineoplastic agents in clinical oncology and the fact that most patients with solid tumors are not cured by standard chemotherapeutic regimens with these agents, this project purposes to assess the potentiation by anguidine of DNA-reactive antineoplastic agents induced cytotoxicity in human transitional cell tumors of the urinary tract and normal cells. The sensitivity of the cells to the various drug treatments will be assessed in an antiproliferation assay, colormetric protein-based assay and a clonogenic assay. The long range goal of this project is to elucidate whether anguidine can be used as a synergistic agent with DNA-reactive antineoplastic drugs in clinical cancer chemotherapy. Such an approach would have clinical benefit in two ways: (1) it could improve the anticancer effect at a given dosage; and (2) it could allow for treatment with relatively lower doses or less frequent application of anticancer agents which are limited by local or systemic toxicities and thereby reduce the toxicity to normal tissues. The undergraduate student's knowledge will be enhanced in cell culture techniques, tumor cell biology, and the pharmacology of antitumor drugs.

安贵定是一种蛋白质合成抑制剂， 植物寄生真菌木贼镰刀菌（Fusarum equiseti）的代谢产物。 安古丁能 优先诱导正常细胞的可逆细胞周期停滞， 肿瘤细胞 这种选择性的细胞周期阻滞提供了优先的 保护正常细胞不受干扰素的细胞毒性 具有S期活性的药物，如阿霉素和1-B-D-阿拉伯呋喃糖基， 胞嘧啶 与S期药物的保护作用相反， 胍能增强DNA-反应性酶的细胞毒性 药物如顺铂、美法仑和博来霉素。 鉴于DNA反应酶的广泛应用， 药物在临床肿瘤学和事实，大多数患者与固体 肿瘤不能通过使用这些药物的标准化疗方案治愈 代理商，本项目的目的是评估增强通过指南的 DNA反应性抑制剂对人的细胞毒性 尿路移行细胞肿瘤和正常细胞。 的 将评估细胞对各种药物治疗的敏感性 在抗增殖测定、基于比色蛋白测定和 克隆形成测定。 这个项目的长期目标是阐明胍是否可以 作为与DNA反应性抗肿瘤药物的协同剂， 临床癌症化疗。 这种方法具有临床意义。 在两个方面受益：（1）它可以提高抗癌效果， （2）它可以允许治疗相对较低的剂量。 剂量或较低频率的抗癌剂的应用是有限的 通过局部或全身毒性，从而将毒性降低至正常 组织中 在细胞培养方面，提高了本科生的知识水平 技术、肿瘤细胞生物学和抗肿瘤药物药理学。