Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, Maryland 20892, USA.
BMC Med Genomics. 2011 May 11;4:38. doi: 10.1186/1755-8794-4-38.
Traditional Chinese Medicine (TCM) has been used for thousands of years to treat or prevent diseases, including cancer. Good manufacturing practices (GMP) and sophisticated product analysis (PhytomicsQC) to ensure consistency are now available allowing the assessment of its utility. Polychemical Medicines, like TCM, include chemicals with distinct tissue-dependent pharmacodynamic properties that result in tissue-specific bioactivity. Determining the mode of action of these mixtures was previously unsatisfactory; however, information rich RNA microarray technologies now allow for thorough mechanistic studies of the effects complex mixtures. PHY906 is a long used four herb TCM formula employed as an adjuvant to relieve the side effects associated with chemotherapy. Animal studies documented a decrease in global toxicity and an increase in therapeutic effectiveness of chemotherapy when combined with PHY906.
Using a systems biology approach, we studied tumor tissue to identify reasons for the enhancement of the antitumor effect of CPT-11 (CPT-11) by PHY906 in a well-characterized pre-clinical model; the administration of PHY906 and CPT-11 to female BDF-1 mice bearing subcutaneous Colon 38 tumors.
We observed that 1) individually PHY906 and CPT-11 induce distinct alterations in tumor, liver and spleen; 2) PHY906 alone predominantly induces repression of transcription and immune-suppression in tumors; 3) these effects are reverted in the presence of CPT-11, with prevalent induction of pro-apoptotic and pro-inflammatory pathways that may favor tumor rejection.
PHY906 together with CPT-11 triggers unique changes not activated by each one alone suggesting that the combination creates a unique tissue-specific response.
中医药（TCM）已有数千年的历史，可用于治疗或预防疾病，包括癌症。现在有良好的生产规范（GMP）和复杂的产品分析（PhytomicsQC）来确保一致性，从而可以评估其效用。像中医药这样的多化学成分药物包含具有独特组织依赖性药效特性的化学物质，从而导致组织特异性生物活性。这些混合物的作用方式以前无法令人满意地确定；但是，信息丰富的 RNA 微阵列技术现在可以对复杂混合物的影响进行彻底的机制研究。PHY906 是一种长期使用的四草药 TCM 配方，用作减轻与化疗相关的副作用的辅助药物。动物研究记录了与 PHY906 联合使用时，整体毒性降低和化疗治疗效果提高。
我们使用系统生物学方法研究肿瘤组织，以确定 PHY906 增强 CPT-11（CPT-11）在经过充分特征描述的临床前模型中的抗肿瘤作用的原因；向携带皮下结肠 38 肿瘤的雌性 BDF-1 小鼠施用 PHY906 和 CPT-11。
我们观察到：1）单独使用 PHY906 和 CPT-11 会引起肿瘤，肝脏和脾脏的明显改变；2）PHY906 单独主要诱导肿瘤中转录和免疫抑制的抑制；3）在 CPT-11 的存在下，这些作用被逆转，普遍诱导促凋亡和促炎途径，这可能有利于肿瘤排斥。
PHY906 与 CPT-11 一起触发了每种药物单独作用时未激活的独特变化，这表明该组合产生了独特的组织特异性反应。
