Center for Herbal Research on Colorectal Cancer

描述(申请人提供)：结直肠癌是美国第二大最常见的癌症，也是癌症相关死亡的第二大原因。植物类药物可能含有抗癌化合物，这些化合物可以单独使用，也可以作为现有化疗的辅助药物，以提高疗效并减少药物引起的毒性。确定草药来源以开发理想的化学预防仍然是推进这种癌症治疗的关键步骤，并将在拟议的项目中解决。目前的提案基于令人信服的初步结果和文献报道，假设来自人参家族的两种特定草药--蒸或未蒸的西洋参和三七根--可能具有显著的抗癌活性。该项目的目的是彻底描述测试草药的抗增殖作用，以及其直接和辅助抗癌作用的潜在作用机制。我们推测，西洋参和三七，特别是经过蒸制后的西洋参和三七，是有效的抗结直肠癌的抗肿瘤和化学辅助化合物。在拟议的项目中，我们将测试这两种人参药材对不同的人结直肠癌细胞株和小鼠异种移植瘤的杀瘤作用，并确定相关的机制。我们将利用细胞系和小鼠模型进一步测试提取物是否增强结肠癌化疗药物5-氟尿嘧啶和伊立替康的杀瘤作用。如果试验草药和化疗药物之间存在协同作用，那么它将能够降低药物剂量，从而减少与剂量相关的毒性。此外，还将确定新发现的清蒸草药活性成分是否会增加化疗药物的活性。最后，化疗药物和测试草药(如果有的话)之间的药代动力学相互作用将被表征。这个项目的一个新奇之处是使用了“击倒”草药提取物，这将使草药提取物的作用与负责的活性成分(S)有更明确的联系。这项拟议研究的数据有可能改善结直肠癌患者的治疗方案和生活质量。

DESCRIPTION (provided by applicant): Colorectal cancer is the second most prevalent cancer and the second leading cause of cancer related death in the United States. Botanicals could potentially have anti-cancer compounds that may be used alone or as adjuncts to existing chemotherapy to improve efficacy and reduce the drug-induced toxicity. Identifying herbal sources to develop ideal chemoprevention remains an essential step in advancing the treatment of this cancer and will be addressed in the proposed project. The current proposal postulates based on convincing preliminary results and literature reports that two specific herbs from the ginseng family, steamed or unsteamed roots of American ginseng and notoginseng, may have significant anti-cancer activities. The aim of this project is to thoroughly characterize the anti-proliferative actions of test herbs and the underlying mechanisms of action in their direct and adjuvant anti-cancer effects. We hypothesize that American ginseng and notoginseng, particularly after steaming preparation, are effective tumoricidal and chemo-adjuvant compounds against human colorectal cancer. In the proposed project, we will test the tumoricidal effects of these two ginseng herbs on distinct human colorectal cancer cell lines and a mouse xenograft model, and determine the involved mechanisms. We will further test whether the extracts potentiate the tumoricidal effects of colon cancer chemotherapeutic agents, 5-fluorouracil and irinotecan, using the cell lines and mouse model. If synergistic interactions between test herbs and chemotherapeutic drugs exist, then it will enable lowering of the drug dose thus reducing the dose-related toxicity. In addition, whether the newly identified active constituents from steamed herbs increase chemotherapeutic agents' activity will be determined. Finally, pharmacokinetic interaction between the chemotherapeutic drugs and the test herbs, if any, will be characterized. A novelty of this project is the use of "knockout" herbal extracts which will allow a more conclusive association of the effect of the herbal extract to the responsible active constituent(s). Data from the proposed study have a potential to improve treatment regimens and the quality of life for patients suffering from colorectal cancer.