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Chemoprevention of lung cancer with red ginseng extracts

红参提取物对肺癌的化学预防

基本信息

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
项目类别：
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

项目摘要

* 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.

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