Ginseng and its Constituents in Complementary Breast Cancer Therapy

描述（由申请人提供）：人参是一种最畅销的草药补充剂，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的提高有关。在我们的初步数据中，我们证明了人参增加了化疗药物阿霉素对乳腺癌细胞的体外和体内肿瘤生长的抗癌功效，并进一步防止了阿霉素治疗引起的体重下降。人参含有超过30种不同的人参皂苷和多糖成分，这些被认为是人参根中的主要生物活性成分。我们提供了初步的证据，人参多糖刺激先天免疫系统，诱导巨噬细胞产生增加的细胞因子释放。反过来，人参皂苷可能直接起到抑制癌细胞增殖的作用。我们对培养的人乳腺癌MCF-7细胞的初步研究表明，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。剩下的是在体内模型中测试这些发现，并确定人参成分如何在阿霉素治疗期间促进人参的补充效果。首先，用人乳腺癌MCF-7细胞接种雌性裸鼠，观察人参对阿霉素抑制肿瘤生长和诱导全身毒性的影响。我们将采用两种治疗模式，一种是在乳腺癌确诊后（化疗前）就开始服用人参，另一种是在化疗开始时开始服用人参。研究结束时，对肿瘤组织进行增殖和凋亡指标分析，对血液进行先天免疫反应激活和全身毒性分析，对心脏组织进行阿霉素治疗相关的心脏毒性分析。最后，人类乳腺上皮细胞和乳腺癌细胞系将用人参皂苷和/或细胞因子处理，以确定可能负责人参诱导对阿霉素治疗致敏的信号传导和凋亡途径。我们假设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有效性。这些数据将为向卫生保健专业人员和公众提供有关人参及其成分丰富提取物在补充乳腺癌治疗中的使用的循证信息提供第一步转化。

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.