Gene Expression Profiling and Pathway Network Analysis Predicts a Novel Antitumor Function for a Botanical-Derived Drug, PG2.

Gene Expression Profiling and Pathway Network Analysis Predicts a Novel Antitumor Function for a Botanical-Derived Drug, PG2.
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DOI:
10.1155/2015/917345
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发表时间:
2015
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Huang CY
Huang CY
中科院分区:
其他
文献类型:
--
作者:
Kuo YL;Chen CH;Chuang TH;Hua WK;Lin WJ;Hsu WH;Chang PM;Hsu SL;Huang TH;Kao CY;Huang CY

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PG2是一种植物药,主要成分为黄芪多糖(APS)。它在造血和缓解癌症相关疲劳方面的作用最近已在癌症患者中进行了临床研究。然而,对其功能的系统分析仍然有限。本研究的目的是使用基于微阵列的表达谱来评估三个不同产品批次的 PG2 的质量和一致性,并研究 PG2 的生物学机制。综合分子分析方法旨在检查 HL-60 白血病细胞中 PG2 诱导的显着特征。通过相关系数的分层聚类对 PG2 的基因表达特征进行定量分析。结果表明,PG2产品批次一致,质量优良。这些批次在调节免疫和造血系统方面的功能也彼此相同。在 PG2 特征中,有 5 个与阿霉素相关的基因:IL-8、MDM4、BCL2、PRODH2 和 BIRC5。此外,PG2和阿霉素的组合对诱导HL-60细胞的细胞死亡具有协同作用。与基于生物信息学的方法一起,基因表达谱为草药的质量和一致性提供了定量测量,并揭示了 PG2 在癌症治疗中的新作用(例如免疫调节)。
PG2 is a botanical drug that is mostly composed of Astragalus polysaccharides (APS). Its role in hematopoiesis and relieving cancer-related fatigue has recently been clinically investigated in cancer patients. However, systematic analyses of its functions are still limited. The aim of this study was to use microarray-based expression profiling to evaluate the quality and consistency of PG2 from three different product batches and to study biological mechanisms of PG2. An integrative molecular analysis approach has been designed to examine significant PG2-induced signatures in HL-60 leukemia cells. A quantitative analysis of gene expression signatures was conducted for PG2 by hierarchical clustering of correlation coefficients. The results showed that PG2 product batches were consistent and of high quality. These batches were also functionally equivalent to each other with regard to how they modulated the immune and hematopoietic systems. Within the PG2 signature, there were five genes associated with doxorubicin: IL-8, MDM4, BCL2, PRODH2, and BIRC5. Moreover, the combination of PG2 and doxorubicin had a synergistic effect on induced cell death in HL-60 cells. Together with the bioinformatics-based approach, gene expression profiling provided a quantitative measurement for the quality and consistency of herbal medicines and revealed new roles (e.g., immune modulation) for PG2 in cancer treatment.
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