The anti-tumor effect and bioactive phytochemicals of Hedyotis diffusa willd on ovarian cancer cells
The anti-tumor effect and bioactive phytochemicals of Hedyotis diffusa willd on ovarian cancer cells
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白花蛇舌草对卵巢癌细胞的抗肿瘤作用及生物活性植物化学物质
DOI：
10.1016/j.jep.2016.07.027
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发表时间：
2016-11-04
影响因子：
5.4
通讯作者：
Li, Weiling
中科院分区：
文献类型：
--
作者：
Zhang, Lin;Zhang, Jing;Li, Weiling
民族药理学相关性：白花蛇舌草（HDW）是中国广泛使用的草药。它具有抗氧化、抗炎、抗癌等多种药理作用。本研究旨在探讨中药高剂量组对卵巢癌A2780细胞的抗肿瘤作用及其机制，并对其中的活性成分进行鉴定。材料与方法：采用MTT法检测高剂量组对卵巢癌A2780细胞活力的影响。采用DAPI染色和流式细胞仪检测细胞凋亡。通过伤口愈合和transwell实验检测HDW对卵巢癌细胞迁移的影响。Western blotting法检测HDW处理后人卵巢癌细胞caspase 3/9、Bcl-2和MMP-2/9蛋白水平的变化。结果：HDW对A2780卵巢癌细胞生长有明显的抑制作用，并能诱导细胞凋亡。HDW诱导细胞凋亡与抗凋亡蛋白Bcl-2的下调和caspase 3/9的激活有关。伤口愈合和transwell小室分析表明HDW抑制卵巢癌细胞的迁移。HDW显著降低MMP-2/9表达。HPLC-TOF-MS分析表明，HDW中含有13种黄酮类化合物和1种蒽醌类化合物，这些化合物可能与HDW的抗肿瘤活性有关。结论：HDW能有效抑制卵巢癌细胞的生长，并通过凋亡途径诱导细胞凋亡。此外，HDW通过下调MMP-2和MMP-9的表达来抑制卵巢癌细胞的迁移。结果表明，HDW对卵巢癌患者具有潜在的治疗作用。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Hedyotis diffusa willd (HDW) is a widely used medicinal herb in China. It processed various medicinal properties including antioxidative, anti-inflamatory and anti-cancer effects. This study aimed to investigate the anti-tumor effects of HDW on ovarian cancer cells and the underlying mechanisms as well as identify the bioactive compounds.Materials and methods: Effects of HDW on the viability of ovarian cancer A2780 cells were detected by MIT assay. Apoptosis was detected by cell morphologic observation through DAPI staining and flow cytometry analysis. The migration of ovarian cancer cells which exposed to HDW were detected by wound healing and transwell assays. The protein levels of caspase 3/9, Bcl-2 and MMP-2/9 in human ovarian cancer cells treated with HDW were assessed by western blotting analysis. The potential bioactive compounds were characterized by HPLC-Q-TOF-MS.Results: HDW significantly inhibited the growth of A2780 ovarian cancer cells and induced apoptosis. The induction of apoptosis by HDW was associated with down-regulation of anti-apoptotic protein Bcl-2 and the activation of caspase 3/9. Wound healing and transwell chamber assays indicated HDW suppressed the migration of ovarian cancer cells. HDW dramatically decreased MMP-2/9 expression. A HPLCQ-TOF-MS analysis of HDW indicated the presence of 13 flavonoids compounds and one anthraquinone compound, which may contribute to the anticancer activity of the HDW.Conclusions: HDW effectively restricted the growth of ovarian cancer cells and induced apoptosis through the mitochondria-associated apoptotic pathway. Furthermore, HDW suppressed the migration of ovarian cancer cells through down-regulation of MMP-2 and MMP-9 expression. These results showed that HDW hold potential therapeutic effect for ovarian cancer patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.