Chemoprevention of lung cancer with red ginseng extracts

红参提取物对肺癌的化学预防

• 批准号: 8133545
• 负责人: MING YOU
• 金额: $ 46.21万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8133545
• 关键词: A/J Mouse; Affinity Chromatography; Alleles; Apoptosis; Biological Assay; Biological Availability; Biological Products; Caco-2 Cells; Cell Proliferation; Cell model; Characteristics; Chemoprevention; Chemopreventive Agent; Clinical Research; Clinical Trials; Deletion Mutation; Development; Dominant-Negative Mutation; Dose; Drug Kinetics; Foundations; Fractionation; Future; Ginseng Preparation; High Pressure Liquid Chromatography; Human; In Vitro; Intestinal Absorption; Lung; Lung Adenocarcinoma; Lung Neoplasms; Malignant neoplasm of lung; Measures; Methods; Modeling; Mus; Mutant Strains Mice; Mutation; Organ; Preventive; Regimen; Research Design; Rodent; Screening procedure; Silicones; Site; Solid; Squamous Cell Lung Carcinoma; Squamous cell carcinoma; Testing; Time; Transgenic Mice; Tumor Cell Line; base; carcinogenesis; experience; in vitro activity; in vivo; liquid chromatography mass spectrometry; lung Carcinoma; lung carcinogenesis; mouse model; mutant mouse model; pre-clinical; preclinical study; prevent; public health relevance; research study; solvent extraction; tumor

* DESCRIPTION (provided by applicant): The overall objective of this proposal is to characterize red ginseng extract (RGE) and its key active components (KAC) preclinically as a potent lung cancer chemopreventive agent. In a preliminary study, we demonstrated a strong efficacy of red ginseng in chemoprevention against lung tumor development in A/J mice. We hypothesize that ginseng will prevent chemically induced lung adenocarcinoma and squamous cell carcinoma formation in a mutant mouse model with genetic changes commonly seen in human lung cancers. Four specific aims are proposed to test this hypothesis. Aim 1 will identify the key active components of red ginseng via in vitro activity- guided fractionation chromatographic separation supplemented by measuring their intestinal absorption potentials. Aim 2 will evaluate the effect of RGE and its KAC on lung adenocarcinoma carcinogenesis in a transgenic mouse lung adenocarcinoma model with genetic changes commonly seen in human lung cancers. Aim 3 will determine the effect of RGE and its KAC on lung squamous cell carcinoma development in p53 mutant mice. Aim 4 will perform pharmacokinetic and biopharmaceutical characterizations of RGE and its KAC. This proposal is timely and significant since future chemoprevention clinical trials of ginseng against lung cancer in humans require vigorous preclinical characterization of its efficacy and biopharmaceutical characteristics such as bioavailability and pharmacokinetic profile. Furthermore, we will use a newly developed mutant mouse lung tumor models of both lung adenocarcinoma and lung squamous cell carcinoma, which shares both histopathological features and genetic alterations observed in human lung carcinogenesis. The results from this proposal will provide a solid foundation for clinical trials of ginseng as a lung cancer chemopreventive agent. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE We propose to characterize red ginseng extracts (RGE) preclinically as a potent lung cancer chemopreventive agent. In vitro experiments have shown that ginseng inhibits cell proliferation and induces apoptosis in tumor cell lines. In vivo, ginseng has been shown to inhibit rodent carcinogenesis in various organ sites including the lung. We will identify the key active components of red ginseng via in vitro activity-guided fractionation chromatographic separation supplemented by measuring their intestinal absorption potentials, evaluate the effect of ginseng on lung carcinogenesis in a transgenic mouse lung carcinoma model with genetic changes commonly seen in human lung cancers, and perform pharmacokinetic and biopharmaceutical characterizations of red ginseng and its key active components. We believe that the proposed studies are significant because future chemoprevention clinical trials of ginseng against lung cancer in humans require vigorous preclinical characterization of its efficacy and biopharmaceutical characteristics such as bioavailability and pharmacokinetic profile.

* 描述（由申请人提供）： 该提案的总体目的是将红色人参提取物（RGE）及其关键活性成分（KAC）临床前临时作为有效的肺癌化学预防剂。在一项初步研究中，我们证明了红色人参在A/J小鼠中针对肺部肿瘤发育的化学预防中具有强大的功效。我们假设人参将在突变小鼠模型中预防化学诱导的肺腺癌和鳞状细胞癌的形成，其遗传变化在人类肺癌中常见。提出了四个特定目标来检验这一假设。 AIM 1将通过测量其肠道吸收潜能补充的体外活性指导色谱分离来鉴定红色人参的关键活性成分。 AIM 2将评估RGE及其KAC对转基因小鼠肺腺癌模型中肺腺癌的影响，其遗传变化在人类肺癌中常见。 AIM 3将确定RGE及其KAC对p53突变小鼠中肺鳞状细胞癌发育的影响。 AIM 4将对RGE及其KAC进行药代动力学和生物药物表征。该建议是及时且重要的，因为人参对人的未来化学预防临床试验需要对其功效和生物药物特征（例如生物利用度和药代动力学特征）进行剧烈的临床前表征。此外，我们将使用新开发的肺腺癌和肺鳞状细胞癌的新开发的突变小鼠肺肿瘤模型，该模型具有组织病理学特征和人类肺癌发生中观察到的遗传学特征。该提案的结果将为人参作为肺癌化学预防剂的临床试验奠定坚实的基础。 公共卫生相关性： 我们建议将红色人参提取物（RGE）临床上描述为有效的肺癌化学预防剂。体外实验表明，人参抑制细胞增殖并诱导肿瘤细胞系的凋亡。在体内，人参已被证明可以抑制包括肺在内的各种器官部位的啮齿动物癌变。我们将通过通过测量其肠道吸收潜能来补充的体外活性引导的分级色谱分离来确定红色人参的关键活性成分，评估人参对肺癌发生的影响，在转传基因小鼠肺癌中，通过在人类肺癌和肺癌中常见的遗传变化，并在人类肺癌中经常出现，并在人类肺癌中表现出遗传变化，并在人类肺癌中表现出遗传，并在人肺癌症中表现出色，并进行了杀伤性的肺癌，并进行了肺癌和生物癌的表现。 成分。我们认为拟议的研究很重要，因为人参对人的未来化学预防临床试验需要对其疗效和生物药物特征（例如生物利用度和药代动力学特征）进行剧烈的临床前表征。