Mechanisms for skin tumor inhibition by caffeine and voluntary exercise

咖啡因和自愿运动抑制皮肤肿瘤的机制

• 批准号: 7104522
• 负责人: Yaoping Lu
• 金额: $ 7.7万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7104522
• 关键词: apoptosis; caffeine; exercise; fats; neoplasm /cancer; skin

DESCRIPTION (provided by applicant): Sunlight-induced skin cancer is the most prevalent cancer in the United States, and appropriate strategies to prevent this cancer would save lives and have significant social impact. In earlier studies, we found that oral administration of caffeine inhibited ultraviolet B light (UVB)-induced skin carcinogenesis in mice. Mechanistic studies indicated a stimulatory effect of caffeine administration on DVB-induced apoptosis in the epidermis and in tumors. Caffeine administration did not affect apoptosis in normal non-UVB irradiated mice or in non-tumor areas of tumor-bearing mice. In a recent studies we treated mice with oral administration of caffeine and found that this treatment with caffeine stimulated locomotor activity and decreased the thickness of dermal fat away from tumors and directly under tumors. An increase in locomotor activity by providing mice with the opportunity for voluntary running wheel exercise also decreased body fat and decreased the thickness of the dermal fat layer. More importantly, voluntary exercise inhibited UVB-induced skin carcinogenesis in mice. This was the first demonstration of skin cancer inhibition by voluntary exercise. We plan to determine the effects of voluntary running wheel exercise on UVB-induced apoptosis and cell proliferation in the epidermis of SKH-1 mice. We will investigate the possible synergistic inhibitory effects of voluntary running wheel exercise in combination with oral administration of caffeine on the formation of nonmalignant and malignant skin tumors in SKH-1 'high risk' mice previously treated chronically with UVB. We will determine the possible synergistic effects of voluntary running wheel exercise in combination with oral administration of caffeine on the levels of apoptosis and cell proliferation in histologically-characterized UVB-induced tumors and in areas of the epidermis away from tumors. The tissue fat levels in these mice will be determined and the relationship between the fat level and the expression of apoptosis and cell proliferation will be analyzed. The proposed studies will provide a better understanding of the mechanisms of cancer prevention by voluntary exercise alone and in combination with caffeine, and these studies may help in the development of a diet/exercise program to prevent cancer

描述（由申请人提供）：阳光引起的皮肤癌是美国最普遍的癌症，预防这种癌症的适当策略将挽救生命并产生重大的社会影响。在较早的研究中，我们发现咖啡因的口服抑制紫外线B光（UVB）诱导的小鼠皮肤致癌作用。机械研究表明，咖啡因对表皮和肿瘤中DVB诱导的凋亡的刺激作用。咖啡因的给药不影响正常非UVB辐照小鼠或肿瘤小鼠的非肿瘤区域的凋亡。在最近的一项研究中，我们用口服咖啡因治疗小鼠，发现这种用咖啡因治疗刺激了运动活性，并降低了皮肤脂肪的厚度，从肿瘤和肿瘤下方直接降低。通过为小鼠提供自愿运动车轮运动的机会，运动活动的增加也减少了体内脂肪并减少了真皮脂肪层的厚度。更重要的是，自愿运动抑制了UVB诱导的小鼠皮肤致癌作用。这是通过自愿运动抑制皮肤癌的首次演示。我们计划确定SKH-1小鼠表皮中UVB诱导的凋亡和细胞增殖的影响。我们将研究自愿跑步轮运动的协同抑制作用以及口服咖啡因对SKH-1“高风险”小鼠的非恶性和恶性皮肤肿瘤的形成，以前用UVB慢性治疗。我们将确定自愿跑步轮运动的可能协同作用以及咖啡因对组织学特征化UVB诱导的肿瘤以及表皮远离肿瘤区域的凋亡和细胞增殖水平的结合。将确定这些小鼠的组织脂肪水平，并将分析脂肪水平与细胞凋亡的表达与细胞增殖之间的关系。拟议的研究将更好地理解单独自愿运动并与咖啡因结合的预防癌症预防机制，这些研究可能有助于制定饮食/运动计划以防止癌症