中国药物警戒 ›› 2023, Vol. 20 ›› Issue (7): 728-734.
DOI: 10.19803/j.1672-8629.20230243

• 中药及其活性成分抗肿瘤作用研究专栏 • 上一篇    下一篇

大黄素-8-O-β-D-葡萄糖苷联合紫杉醇抑制人乳腺癌细胞活力及侵袭转移的研究

严亦舒, 赵岩△, 卢天公, 孙震晓*   

  1. 北京中医药大学生命科学学院,北京 102488
  • 收稿日期:2023-04-19 出版日期:2023-07-15 发布日期:2023-07-14
  • 通讯作者: *孙震晓,女,教授,中药分子细胞药理学与毒理学。E-mail：sunzx@bucm.edu.cn
  • 作者简介:严亦舒,女,在读硕士,中药及其活性成分抗肿瘤药效及机制研究。△为并列第一作者。
  • 基金资助:
    国家自然科学基金资助项目（81473418,8210- 4460）; 北京中医药大学“揭榜挂帅”项目（2022-JYB-JBZR- 022,2022-JYB-JBZR-023,2022-2025）

Emodin -8-O-β-D-glucoside combined with paclitaxel inhibits the viability and metastasis of human breast cancer cells

YAN Yishu, ZHAO Yan△, LU Tiangong, SUN Zhenxiao*   

  1. School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China
  • Received:2023-04-19 Online:2023-07-15 Published:2023-07-14

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摘要： 目的 探究大黄素-8-O-β-D-葡萄糖苷（EG）与紫杉醇（PTX）联合抗人乳腺癌细胞活力及侵袭转移作用。方法 MTT法检测EG、PTX单独及联合作用对人乳腺癌MCF 7、MDA-MB-231细胞活力的影响,以联合指数（CI）值判断药物联合作用效应;Transwell实验检测两药联用对人乳腺癌细胞侵袭转移能力的影响;实时荧光定量PCR（RT-qPCR）检测转移相关基因mRNA表达水平。结果 EG和PTX均能明显抑制人乳腺癌MCF 7、MDA-MB-231的细胞存活（P<0.01）,在实验浓度下两药联用具有协同效应;EG（240 mmol·L-1）、PTX（5 nmol·L-1）联合用药可明显抑制人乳腺癌细胞的侵袭转移（P<0.01）;两药联用能明显下调人乳腺癌细胞中基质金属蛋白酶基因MMP2、MMP9（P<0.01）,EMT相关基因Vimentin（P<0.01）和Snail（P<0.01,P<0.05）的转录水平,上调CDH1（MCF 7细胞）和下调CDH2（MDA-MB-231细胞）基因的转录水平（P<0.01）。结论 EG与PTX联用可协同抑制人乳腺癌细胞活力及侵袭转移。

关键词: 大黄素-8-O-β-D-葡萄糖苷, 紫杉醇, 联合用药, 人乳腺癌细胞, 侵袭转移, 基质金属蛋白酶, 上皮-间充质转化

Abstract: Objective To investigate the effects of emodin-8-O-β-D-glucoside (EG) combined with paclitaxel (PTX) on the viability and metastasis of human breast cancer cells. Methods MTT assay was used to detect the cell viability of EG, PTX alone and concomitant administration on MCF 7 and MDA-MB-231 cells, and the combination index (CI) value was calculated to evaluate the effects of the two drugs; Transwell assay was used to detect the metastasis ability of the two drugs combinations on two kinds of breast cancer cells; The mRNA expression level of metastasis-associated genes (MMP2、MMP9, CDH1, CDH2, Vimentin and Snail) detected by Quantitative Real-time PCR. Results EG and PTX significantly inhibit the survival of human breast cancer MCF 7 and MDA-MB-231 cells (P<0.01), and the two drugs exhibited a synergistic effect at experimental concentrations; The combination of EG (240 mmol·L-1) and PTX (5 nmol·L-1) can substantially suppress the metastasis of human breast cancer cells (P< 0.01); the expressions of matrix metalloproteinase genes MMP-2 and MMP-9 (P<0.01), EMT-related genes Vimentin (P<0.01) and Snail (P<0.01, P<0.05) in breast cancer cells was significantly down-regulated through the combination of two drugs; the combination can up-regulated the expression level of CDH1 in MCF 7 cells and down-regulated the expression level of CDH2 in MDA-MB-231 cells (P<0.01). Conclusion EG combined with PTX can synergistically inhibit the viability and metastasis of human breast cancer cells.

Key words: emodin-8-O-β-D-glucopyranoside, paclitaxel, combination of drugs, human breast cancer cell, metastasis, matrix metalloproteinases (MMPs), epithelial-mesenchymal transition (EMT)

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