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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

The anti-tumor effect and bioactive phytochemicals of Hedyotis diffusa willd on ovarian cancer cells.

作者信息

Zhang Lin, Zhang Jing, Qi Bing, Jiang Guoqiang, Liu Jia, Zhang Pei, Ma Yuan, Li Weiling

机构信息

Academy of Integrative Medicine, Dalian Medical University, Dalian 116044, China.

Department of Biotechnology, Dalian Medical University, Dalian 116044, China.

出版信息

J Ethnopharmacol. 2016 Nov 4;192:132-139. doi: 10.1016/j.jep.2016.07.027. Epub 2016 Jul 15.

DOI:10.1016/j.jep.2016.07.027
PMID:27426510
Abstract

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 MTT 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 HPLC-Q-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.

摘要

民族药理学相关性

白花蛇舌草是中国广泛使用的草药。它具有多种药用特性,包括抗氧化、抗炎和抗癌作用。本研究旨在探讨白花蛇舌草对卵巢癌细胞的抗肿瘤作用及其潜在机制,并鉴定其生物活性化合物。

材料与方法

采用MTT法检测白花蛇舌草对卵巢癌A2780细胞活力的影响。通过DAPI染色的细胞形态学观察和流式细胞术分析检测细胞凋亡。采用伤口愈合试验和Transwell试验检测暴露于白花蛇舌草的卵巢癌细胞的迁移情况。通过蛋白质印迹分析评估用白花蛇舌草处理的人卵巢癌细胞中caspase 3/9、Bcl-2和MMP-2/9的蛋白水平。通过HPLC-Q-TOF-MS对潜在的生物活性化合物进行表征。

结果

白花蛇舌草显著抑制A2780卵巢癌细胞的生长并诱导细胞凋亡。白花蛇舌草诱导的细胞凋亡与抗凋亡蛋白Bcl-2的下调和caspase 3/9的激活有关。伤口愈合试验和Transwell小室试验表明白花蛇舌草抑制卵巢癌细胞的迁移。白花蛇舌草显著降低MMP-2/9的表达。对白花蛇舌草的HPLC-Q-TOF-MS分析表明存在13种黄酮类化合物和1种蒽醌类化合物,这可能有助于白花蛇舌草的抗癌活性。

结论

白花蛇舌草通过线粒体相关凋亡途径有效抑制卵巢癌细胞的生长并诱导细胞凋亡。此外,白花蛇舌草通过下调MMP-2和MMP-9的表达抑制卵巢癌细胞的迁移。这些结果表明白花蛇舌草对卵巢癌患者具有潜在的治疗作用。

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