Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Int J Gynecol Cancer. 2012 Jul;22(6):960-7. doi: 10.1097/IGC.0b013e318258509d.
Most women with advanced-stage epithelial ovarian cancer (OVCA) ultimately develop chemoresistant recurrent disease. Therefore, a great need to develop new, more active, and less toxic agents and/or to optimize the efficacy of existing agents exists.
In this study, we investigated the activity of Avemar, a natural, nontoxic, fermented wheat germ extract (FWGE), against a range of OVCA cell lines, both alone and in combination with cisplatin chemotherapy and delineated the molecular signaling pathways that underlie FWGE activity at a genome-wide level.
We found that FWGE exhibited significant antiproliferative effects against 12 human OVCA cell lines and potentiated cisplatin-induced apoptosis. Pearson correlation of FWGE sensitivity and gene expression data identified 2142 genes (false discovery rate < 0.2) representing 27 biologic pathways (P < 0.05) to be significantly associated with FWGE sensitivity. A parallel analysis of genomic data for 59 human cancer cell lines matched to chemosensitivity data for 2,6-dimethoxy-p-benzoquinone, a proposed active component of FWGE, identified representation of 13 pathways common to both FWGE and 2,6-dimethoxy-p-benzoquinone sensitivity.
Our findings confirm the value of FWGE as a natural product with anticancer properties that may also enhance the activity of existing therapeutic agents. Furthermore, our findings provide substantial insights into the molecular basis of FWGE's effect on human cancer cells.
大多数晚期上皮性卵巢癌(OVCA)患者最终会发展为耐药性复发性疾病。因此,迫切需要开发新的、更有效和毒性更小的药物,或者优化现有药物的疗效。
本研究我们调查了 Avemar(一种天然、无毒、发酵的小麦胚芽提取物)对一系列 OVCA 细胞系的活性,包括单独使用以及与顺铂化疗联合使用,并在全基因组水平上阐明了 Avemar 活性的分子信号通路。
我们发现 Avemar 对 12 个人类 OVCA 细胞系表现出显著的抗增殖作用,并增强了顺铂诱导的细胞凋亡。Avemar 敏感性与基因表达数据的 Pearson 相关性分析确定了 2142 个基因(错误发现率<0.2),代表 27 个生物学途径(P<0.05)与 Avemar 敏感性显著相关。对 59 个人类癌细胞系的基因组数据进行平行分析,并与 2,6-二甲氧基-p-苯醌(Avemar 的一种拟议有效成分)的化疗敏感性数据相匹配,确定了 13 个途径在 Avemar 和 2,6-二甲氧基-p-苯醌敏感性中都有代表性。
我们的研究结果证实了 Avemar 作为一种具有抗癌特性的天然产物的价值,它也可能增强现有治疗药物的活性。此外,我们的研究结果为 Avemar 对人类癌细胞的作用的分子基础提供了重要的见解。