ALTERATIONS IN ANTICANCER DRUG ACTIVITY BY ANGUIDINE

安圭定是一种蛋白质合成抑制剂，是植物毒性的主要成分。 植物寄生菌Fusarum equiseti的代谢产物。安圭定可以 优先诱导正常对照可逆性细胞周期停滞 肿瘤细胞。这种选择性的细胞周期停滞提供了优先考虑 正常细胞对抗肿瘤药物细胞毒性的保护作用 具有S相活性的药物，如阿霉素和1-B-D-阿拉伯呋喃葡萄糖- 胞嘧啶。与S相剂的保护作用相比， 金刚烷可增强DNA反应性抗肿瘤药物的细胞毒作用 顺铂、马法兰和博莱霉素等药物。 鉴于DNA反应性抗肿瘤药物的广泛应用 临床肿瘤学的药物和事实是大多数患者固体 使用这些药物的标准化疗方案不能治愈肿瘤 试剂，本项目的目的是评估异丙肾上腺素对 DNA反应性抗肿瘤药物对人体的细胞毒作用 尿路移行细胞瘤和正常细胞。这个 将评估细胞对各种药物治疗的敏感性。 在抗增殖试验中，基于蛋白质的比色分析和 克隆形成试验。 这个项目的长期目标是阐明安非他定是否可以 作为DNA反应性抗肿瘤药物的增效剂 临床癌症化疗。这样的方法将在临床上 好处有两个方面：(1)它可以同时提高抗癌效果 给予一定的剂量；(2)可以用相对较低的剂量进行治疗 使用剂量或使用频率有限的抗癌药物 局部或全身毒性，从而降低对正常的毒性 纸巾。 本科生的知识将在细胞培养中得到加强 技术、肿瘤细胞生物学和抗肿瘤药物的药理学。

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.