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Prevention of solar UV-induced skin cancer by targeting LTA4H

通过靶向 LTA4H 预防太阳紫外线诱发的皮肤癌

基本信息

批准号：
9114539
负责人：
Zigang Dong
金额：
$ 34.88万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-22 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9114539
关键词：
Actinic keratosis Aminopeptidase Anabolism Animal Model Anthracenes Arachidonic Acids Basal cell carcinoma Binding Biological Cancer Cell Growth Cell Death Cell Line Cell Respiration Characteristics Chemoprevention Chemopreventive Agent Chronic Colon Carcinoma Data Development Enzymes Erythema Exhibits Growth Health Hormones Human Incidence Inflammation Inflammatory Inflammatory Response Knockout Mice Lesion Leukotriene B4 Leukotrienes Light Malignant Epithelial Cell Malignant Neoplasms Malignant neoplasm of pancreas Modeling Mus Neoplastic Cell Transformation PTCH gene Pathology Peptides Physiological Pigmentation physiologic function Play Prevention Process Production Reporting Resveratrol Role Signal Pathway Skin Skin Cancer Skin Carcinogenesis Squamous cell carcinoma Staging Structure Suggestion Sunscreening Agents Testing Tetradecanoylphorbol Acetate The Sun Tumor Promoters UV induced Ultraviolet Rays Zinc base cancer therapy cancer type carcinogenesis cell growth dimethylbenzanthracene drug development in vivo inhibitor/antagonist leukotriene A4 hydrolase mouse model pancreatic cancer cells paracrine protein expression response skin cancer prevention sun damage ultraviolet irradiation

项目摘要

DESCRIPTION (provided by applicant): Skin cancer is the most common human cancer and the number one cancer in terms of incidence in the USA. Ultraviolet (UV) irradiation in solar light elicits various biological responses in the skin, including inflammation, pigmentation, erythema, and cell death, and therefore the role of UV light as a major etiologic factor is of particular concern. The use of sunscreens or sun blocks has not been effective in preventing skin cancer, and therefore new mechanism-based approaches are critically needed to treat UV-induced skin cancer. This project is aimed toward investigating the role of leukotriene A4 hydrolase (LTA4H) in solar ultraviolet (UV) - induced skin carcinogenesis. LTA4H was shown to exhibit high levels of protein expression in certain types of cancers and its inhibition leads to a reduced cancer incidence in various animal models. Importantly, our preliminary data indicate that suppressing LTA4H expression and activity decreases skin carcinogenesis in the 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) two-stage mouse skin carcinogenesis model. We also reported that [6]-gingerol or resveratrol binds with LTA4H to suppress colon or pancreatic cancer cell growth, respectively, in vivo. We hypothesize that inhibition of LTA4H by [6]-gingerol or resveratrol will result in suppression of solar UV-induced skin carcinogenesis.