Androgenic And Antiandorgenic Interactions Of PC-SPES

PC-SPES 的雄激素和抗雄激素相互作用

• 批准号: 6359848
• 负责人: CHARLES E. ROSELLI
• 金额: $ 18.88万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6359848
• 关键词: alternative medicine; androgen receptor; aromatase; biological signal transduction; cytochrome P450; high performance liquid chromatography; histology; hormone regulation /control mechanism; laboratory rat; medicinal plants; neoplasm /cancer chemotherapy; prostate neoplasms; testosterone

DESCRIPTION (provided by applicant): The Chinese herbal preparation designated PC-SPES, which is comprised of a mixture of the extracts of eight different herbs, is gaining increasing acceptance as a complimentary or alternative treatment for prostate cancer because of its ability to arrest tumor growth. The overall goal of this proposal is to understand the mechanism(s) by which PC-SPES acts to inhibit prostate cell growth. Our preliminary study in rats, demonstrated that PC-SPES could significantly reduce prostate weight, while also reducing circulating testosterone levels. Based on these results and reports in the literature, we hypothesize that PC-SPES has potent antiandrogenic effects that are exerted at several potential sites (e.g., CNS, testis, and prostate), and through several potential mechanisms (e.g., androgen synthesis, receptor activation, or metabolism). In this way, the individual herbal components of PC-SPES may act synergistically to exert anti-tumor actions that may be more effective than those produced by any single treatment modality or site of action. Thus, it is our intention to study the mechanism of action of PC-SPES in all of its complexity rather than examine the biological actions of its individual components. Our work will identify the sites and potential antiandrogenic actions of PC-SPES, which are undoubtedly causal factors in its apparent anti-tumor effects. To test our hypothesis, we will employ biochemical and histological techniques together with an HPLC-analyzed preparation of PC-SPES to systematically address the following specific aims: Specific Aim 1: To evaluate the time- and dose-dependent effects of orally administered PC-SPES on prostate weight and histology and on sex steroid and gonadotropin levels, in an effort to elucidate the potential mechanism(s) of action of PC-SPES on prostate growth and pathology. Specific Aim 2: To correlate the effects of PC-SPES on prostate growth with 5a-reductase, aromatase, and androgen receptor concentrations, in order to determine the level(s) at which PC-SPES interacts with the androgen-signaling pathway. Specific Aim 3: To evaluate the effect of PCSPES on Cytochrome P450-mediated metabolism of androgenic and antiandrogenic drugs by the liver, in order to identify possible interactions of PC-SPES with other hormone therapies.

描述（由申请人提供）：指定的中草药制剂 PC-SPE，由八种不同提取物的混合物组成 草药，正在越来越多地接受作为免费或替代品的接受 前列腺癌的治疗，因为它具有阻止肿瘤生长的能力。 该提议的总体目标是了解 PC-SPE的作用可抑制前列腺细胞的生长。我们在大鼠的初步研究， 证明PC-SPE可以显着降低前列腺重量，而 还降低了循环睾丸激素水平。基于这些结果， 文献中的报道，我们假设PC-SPE有效 施加在多个潜在部位的抗雄激素作用（例如，CNS， 睾丸和前列腺），以及通过几种潜在机制（例如，雄激素 合成，受体激活或代谢）。这样，个人 PC-SPE的草药成分可能协同作用以发挥抗肿瘤 与任何单一治疗方法相比，可能更有效的动作 方式或行动地点。因此，我们的意图是研究 PC-SPE的所有复杂性的作用，而不是检查生物学 其各个组件的作用。我们的工作将确定网站， PC-SPE的潜在抗雄激素作用无疑是因果关系 其明显的抗肿瘤作用的因素。为了检验我们的假设，我们将 采用生化和组织学技术以及HPLC分析 制备PC SPES以系统地解决以下特定目的： 特定目的1：评估口服的时间和剂量依赖性效果 对前列腺体重和组织学以及性类固醇和性类固醇的管理PC-SPE和 促性腺激素水平，以阐明 PC-SPE对前列腺生长和病理的作用。具体目标2： 将PC-SPE对前列腺生长的影响与5A还原酶的影响相关联， 芳香酶和雄激素受体浓度，以确定 PC-SPE与雄激素信号途径相互作用的水平。 特定目的3：评估PCSPE对细胞色素P450介导的影响 肝脏的雄激素和抗雄激素药物的代谢，以便 确定PC-SPE与其他激素疗法的可能相互作用。