Adjuvant Ginseng Use During Breast Cancer Drug Therapy

说明（申请人提供）：人参是一种被人类广泛用于治疗体力不足、食欲不振、恶病质和阳痿的草药。在亚洲医学中，人参是用于治疗癌症（包括乳腺癌）的草药中的常见成分。最近有科学证据表明，人参及其皂苷成分在体外有效抑制乳腺癌细胞增殖和体内肿瘤生长。因此，许多患者可能在标准化疗和激素治疗方案治疗期间服用人参补充剂，以提高治疗效果并改善癌症化疗药物的副作用。然而，目前还没有关于人参辅助使用如何影响癌症治疗药物疗效的信息。R21提案将解决以下问题。人参的辅助使用是否有助于或干扰标准的乳腺癌化疗或激素治疗？参佐剂对乳腺癌化疗患者是否有缓解作用？为了回答这些问题，我们将研究大剂量范围的个体化疗（阿霉素、环磷酰胺、紫杉醇）或激素（他莫昔芬）治疗药物，单独使用或与西洋参提取物联合使用，对体外人乳腺癌细胞（MCF-7、MDA-MB-231）增殖的影响。这项研究的结果将使我们能够确定辅助人参治疗是否会改变标准癌症治疗药物的疗效。根据这些结果，我们将确定治疗方案，在接种MCF-7或MDA-MB- 231细胞的雌性胸腺裸鼠体内进行测试，监测肿瘤生长、总体健康状况和全身毒性。这些临床前研究将使我们能够确定在接受强效癌症治疗药物的动物中伴随人参治疗可能产生的潜在姑息作用。第三，我们将研究人参/化疗联合治疗对参与细胞周期调节、细胞凋亡和细胞毒性的通路特异性基因/蛋白质的潜在加性、增效或亚加性作用。总之，这些研究的结果将使我们更好地了解西洋参，并将使乳腺癌患者及其医生在标准化疗期间补充使用人参的决策基于证据。

DESCRIPTION (provided by applicant): Ginseng is an herb widely used by humans to treat lack of stamina, loss of appetite and cachexia, and impotence. In Asian medicine, ginseng is a common component in herbals used in treatment of cancer, including breast cancer. There is recent scientific evidence that ginseng and its ginsenoside components are effective in inhibiting breast cancer cell proliferation in vitro and tumor growth in vivo. Consequently, many patients may be taking ginseng supplements during treatment with standard chemotherapy and hormonal therapy regimens in an effort to enhance therapeutic results as well as ameliorate side effects of the cancer chemotherapeutic drugs. However, there is no information on how adjuvant ginseng use could influence the efficacy of the cancer therapeutic drugs. This R21 proposal will address the following questions. Will the adjuvant use of ginseng aid in or interfere with standard breast cancer chemo- or hormonal therapy? Will adjuvant ginseng use produce palliative effects in the breast cancer patient undergoing chemotherapy? To answer these questions, we will examine the effects of a wide dose-range of individual chemotherapy (doxorubicin, cyclophosphamide, paclitaxel) or hormonal (tamoxifen) therapy drugs, alone and in combinations with an extract of American ginseng, on the proliferation of human breast cancer cells (MCF-7, MDA-MB-231) in vitro. The results of this study will allow us to determine if adjuvant ginseng treatment alters the efficacy of standard cancer therapeutic drugs. From these results, we will determine the treatment regimens to be tested in vivo in female athymic nude mice inoculated with either MCF-7 or MDA-MB- 231 cells, monitoring tumor growth as well as general well-being and systemic toxicity. These preclinical studies will allow us to determine the potential palliative effects concomitant ginseng treatment may have in animals receiving the potent cancer therapeutic drugs. Thirdly, we will examine potential additive, synergistic or sub-additive effects of combination ginseng/chemotherapy treatment on pathway-specific genes/proteins involved in cell cycle regulation, apoptosis and cytotoxicity. Together, the results of these studies will provide us with a better understanding of American ginseng and will allow evidence-based decisions to be made by breast cancer patients and their physicians regarding complementary ginseng use during standard chemotherapy.