CHEMOPREVENTION OF LUNG SQUAMOUS CELL CARCINOMA WITH POLYPHENON E

多苯酚 E 化学预防肺鳞状细胞癌

• 批准号: 8308675
• 负责人: YIAN WANG
• 金额: $ 27.78万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-10 至 2013-11-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8308675
• 关键词: Chemoprevention; Chemopreventive Agent; Clinical Chemoprevention; Clinical Trials; Data; Development; Dysplasia; Epigallocatechin Gallate; Exhibits; Foundations; Goals; Green tea; Human; Hyperplasia; Inbred Strains Mice; Lung Adenocarcinoma; Malignant neoplasm of lung; Mediating; Modeling; Molecular; Mouse Strains; Mus; Polyphenon E; Preparation; Rattus; Solid; Squamous Cell Lung Carcinoma; Testing; Transcription Factor AP-1; Transgenic Mice; abstracting; cancer chemoprevention; carcinogenesis; inhibitor/antagonist; innovation; lung Carcinoma; mouse model; mutant; mutant mouse model; pre-clinical; prevent

ABSTRACT Although many mouse models of lung adenocarcinoma exist, there is no mouse lung squamous cell carcinoma model that has been validated for use in preclinical lung cancer chemoprevention studies. Since most clinical chemoprevention trials of lung cancer are performed in subjects with bronchial dysplasia, development of a lung squamous cell carcinoma mouse model becomes one of the highest priorities. We have shown that lung squamous cell carcinomas can be induced chemically in several strains of mice (Wang et al. 2004) and that green tea polyphenols exhibit a significant efficacy against the development of lung squamous cell carcinomas (preliminary data section). In this proposal, we will use a standardized green tea preparation called Polyphenon E (PE) and its major component, EGCG. The overall objective of this proposal is to determine the efficacy of green tea polyphenols in a mouse lung squamous cell carcinoma model and to determine the molecular mechanism that underlies the efficacy of green tea polyphenols in this new mouse model. We hypothesize that green tea polyphenols will prevent chemically induced lung squamous cell carcinoma development and progression in a mutant p53 mouse model, and the chemopreventive effect of green tea polyphenols is, in part, mediated by AP-1. Three aims were proposed to test this hypothesis. Aim 1 will evaluate the effect of green tea polyphenols on lung squamous cell carcinoma carcinogenesis in a p53 mutant transgenic mouse lung carcinoma model. Aim 2 will determine if blockade of AP-l activity will inhibit lung squamous cell carcinoma development and determine if AP-l activity is required for the chemopreventive efficacy of green tea polyphenols. Aim 3 will perform phenotypic profiling of green tea polyphenols' efficacy against lung squamous cell carcinoma development in inbred strains of mice. The results from this proposal will provide a solid foundation for clinical trials of green tea polyphenols as a lung cancer chemopreventive agent.

抽象的 尽管存在许多肺腺癌的小鼠模型，但没有小鼠肺鳞状细胞 已验证用于临床前肺癌化学预防研究的癌模型。 由于大多数肺癌的临床化学预防试验都是在支气管的受试者中进行的 发育不良，肺鳞状细胞癌小鼠模型的发展成为最高的 优先事项。我们已经表明，肺鳞状细胞癌可以在几个 小鼠的菌株（Wang等，2004）和绿茶多酚对针对 肺鳞状细胞癌的发展（初步数据部分）。在这个建议中，我们 将使用称为Polyphenon E（PE）及其主要成分的标准化绿茶制剂， EGCG。该提案的总体目的是确定绿茶多酚在 小鼠肺鳞状细胞癌模型，并确定分子机制 在这种新的小鼠模型中，绿茶多酚的功效是基础。我们假设那个绿色 茶多酚将防止化学诱导的肺鳞状细胞癌发育和 突变体p53小鼠模型的进展以及绿茶多酚的化学预防作用 在某种程度上是由AP-1介导的。提出了三个目的来检验这一假设。 AIM 1将评估 绿茶多酚对p53突变体中肺鳞状细胞癌发生的影响 转基因小鼠肺癌模型。 AIM 2将确定AP-L活性的阻滞是否会抑制 肺鳞状细胞癌发育，并确定是否需要AP-L活性 绿茶多酚的化学预防功效。 AIM 3将执行绿色的表型分析 茶多酚针对肺鳞状细胞癌发育的疗效 老鼠。该提案的结果将为绿茶的临床试验提供坚实的基础 多酚作为肺癌化学预防剂。