A traditional Chinese medicine formulation consisting of Rhizoma Corydalis and Rhizoma Curcumae exerts synergistic anti-tumor activity

A traditional Chinese medicine formulation consisting of Rhizoma Corydalis and Rhizoma Curcumae exerts synergistic anti-tumor activity
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DOI:
10.3892/or_00000539
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发表时间:
2009-11-01
期刊:
影响因子:
4.2
通讯作者:
Wang, Yi-Tao
Wang, Yi-Tao
中科院分区:
医学3区
文献类型:
--
作者:
Gao, Jian-Li;He, Tong-Chuan;Wang, Yi-Tao

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抗癌药物的协同作用分析是临床联合治疗中确定药物比例和剂量的重要手段。然而,该方法很少用于中药制剂的成分评价。延胡索散(YHSS)是宋代(公元960-1279年)以来的一种古老的中药方剂,由延胡索和莪术组成。我们先前已经证明,无论是延胡索还是鹅珠都有很强的抗癌作用。在此,我们试图确定这两种中药之间可能的协同作用。采用四甲基偶氮唑盐比色法测定各中草药提取物及两种提取物在不同剂量比下的IC50。通过等值线图和组合指数(CI)分析,评价不同比例的延胡索和鹅术的协同效应。结果表明,两种中草药提取物按3:2比例配伍,抗肿瘤细胞增殖作用最强。Boyden小室实验、流式细胞仪和荧光显微镜分析发现,E3Y2能显著降低细胞侵袭能力,诱导细胞色素c释放,而不是单次使用,但不影响细胞周期分布。Western印迹法检测ERK1/2、p-ERK1/2和p-Rb的表达,发现E3Y2对p-ERK的表达有明显的抑制作用。因此,我们的研究为莪术和延胡索的协同抗肿瘤作用提供了可信的分子基础。
Synergy analysis of anticancer agents is an important approach to determining the ratio and/or dose of drugs for clinical combination therapy. However, this method is rarely used to evaluate the composition of traditional Chinese medicine formulation. 'Yanhusuo San' (YHSS), which consists of yanhusuo (Rhizoma Corydalis) and Ezhu (Rhizoma Curcumae), has been an archaic Chinese medicine prescription since the Song dynasty (960-1279 AD). We previously demonstrated that either yanhusuo or ezhu has strong anticancer effect. Herein, we sought to determine the possible synergic effect between these two Chinese herbs. We measured the IC50 of each herb extract and both extracts at different ratios of doses by MTT assay. Isobologram and combination index (CI) analyses were used to evaluate the synergistic effect of yanhusuo and ezhu in different fixed ratios. Our results indicated that a combination of two herbal extracts exhibits the strongest anticancer cell proliferation effect at the ratio of 3:2 (ezhu to yanhusuo; referred to as E3Y2). Using Boyden Chamber assay, flow cytometry, and fluorescence microscopy analysis, we found that E3Y2 could markedly reduce the cell invasion ability and induce cytochrome c release rather than single use, but E3Y2 could not influence the cell cycle distribution. When the levels of ERK1/2, p-ERK1/2 and p-Rb were determined by Western blot analysis, we found that the E3Y2 significantly suppresses the level of p-ERK. Thus, our studies provide a plausible molecular basis of the synergistic anti-tumor effect of ezhu and yanhusuo.