Ginseng and its Constituents in Complementary Breast Cancer Therapy

描述（由申请人提供）：人参是一种畅销的草药补充剂，据称可以增加活力和改善健康，因此被癌症患者用作补充疗法。有一些报道称，人参的使用可能与乳腺癌患者的生存率和生活质量增加有关。在我们的初步数据中，我们证明了人参增加了化疗阿霉素对体外乳腺癌细胞和体内肿瘤生长的抗癌功效，并进一步防止了与阿霉素治疗相关的体重减轻。人参含有超过30种不同的皂苷和多糖成分，这些被认为是人参根中的主要生物活性成分。我们提供的初步证据表明，人参多糖刺激先天免疫系统，诱导巨噬细胞产生增加细胞因子的释放。反过来，黄芪皂苷可以直接抑制癌细胞增殖。我们使用培养的人乳腺癌MCF-7细胞进行的初步研究表明，细胞因子和人参皂苷可能共同负责人参发挥抗癌作用的能力。剩下的就是在体内模型中测试这些发现，并确定人参的成分如何在多柔比星治疗期间对人参的补充有效性做出贡献。首先，将用人乳腺癌MCF-7细胞接种雌性裸鼠，并测量补充人参对阿霉素防止肿瘤生长和诱导全身毒性的能力的影响。我们将利用两种治疗模式，旨在模拟一旦诊断出乳腺癌（化疗前）就开始服用人参的个体，或者在化疗开始时开始服用人参的个体。在研究结束时，将分析肿瘤组织的增殖和凋亡指数，分析血液的先天免疫应答激活和全身毒性，并分析心脏组织与阿霉素治疗相关的心脏毒性。最后，人乳腺上皮和乳腺癌细胞系将用人参皂苷和/或细胞因子处理，以确定可能导致人参诱导的对阿霉素治疗的敏化的信号传导和凋亡途径。我们推测，人参的生物活性成分将通过不同的作用机制协同作用，以最大限度地提高人参的安全性和互补性。这些数据将为医疗保健专业人员和公众提供关于在补充乳腺癌治疗中使用人参及其成分富集提取物的循证信息提供第一步。. 公共卫生相关性：该R21赠款项目将确定人参的皂苷和人参多糖成分如何在裸鼠模型中对多柔比星治疗乳腺癌期间人参的互补有效性做出贡献;其次，解决人参成分的作用机制。我们的假设是，这些生物活性人参成分通过不同的作用机制共同发挥作用，以最大限度地提高人参的安全性和互补性。这些数据将为医疗保健专业人员和公众提供关于在补充乳腺癌治疗中使用人参及其成分富集提取物的循证信息提供第一步。

DESCRIPTION (provided by applicant): Ginseng is a top-selling herbal supplement that is purported to increase vitality and improve health and, consequently, is used as a complementary therapy by cancer patients. There are some reports that ginseng use may be associated with increased survival and quality of life in breast cancer patients. In our preliminary data, we demonstrate that ginseng increases the anti-cancer efficacy of the chemotherapeutic doxorubicin on breast cancer cells in vitro and on tumor growth in vivo, and further prevents the weight loss associated with doxorubicin treatment. Ginseng contains over 30 different ginsenosides and polysaccharide components and these are considered the major bioactive constituents in the ginseng root. We provide preliminary evidence that ginseng polysaccharides stimulate the innate immune system and induce macrophages to produce increased cytokine release. In turn, the ginsenosides may act directly to inhibit cancer cell proliferation. Our preliminary studies using cultured human breast cancer MCF-7 cells show that together the cytokines and ginsenosides may be responsible for the ability of ginseng to exert anti-cancer effects. What remains is to test these findings in an in vivo model and determine how ginseng's constituents contribute to the complementary effectiveness of ginseng during doxorubicin treatment. First, female nude mice will be inoculated with human breast cancer MCF-7 cells and the effects of supplemental ginseng on the ability of doxorubicin to prevent tumor growth and induce systemic toxicity will be measured. We will utilize two treatment paradigms that are designed to simulate the individual who starts taking ginseng as soon as the breast cancer is diagnosed (pre-chemotherapy), or the individual who starts taking ginseng when chemotherapy is initiated. At the end of the study, tumor tissues will be analyzed for proliferation and apoptotic indices, blood for activation of innate immune responses and systemic toxicity, and heart tissue will be analyzed for cardiotoxicity associated with doxorubicin treatment. Lastly, human mammary epithelial and breast cancer cell lines will be treated with ginsenosides and/or cytokines to determine the signaling and apoptotic pathways that may be responsible for ginseng-induced sensitization to doxorubicin therapy. We hypothesize that the bioactive ginseng constituents will act in concert through different mechanisms of action to maximize the safety and complementary effectiveness of ginseng. These data will provide the first translational step towards providing evidence-based information to heath care professionals and the public regarding the use of ginseng and its constituent-enriched extracts in complementary breast cancer therapy. . PUBLIC HEALTH RELEVANCE: This R21 grant project will determine how ginseng's ginsenoside and ginseng polysaccharide constituents contribute to the complementary effectiveness of ginseng during doxorubicin treatment for breast cancer in a nude mouse model; and, secondly, address the mechanisms of action of ginseng's constituents. It is our hypothesis that these bioactive ginseng constituents act together through different mechanisms of action to maximize the safety and complementary effectiveness of ginseng. These data will provide the first translational step towards providing evidence-based information to heath care professionals and the public regarding the use of ginseng and its constituent-enriched extracts in complementary breast cancer therapy.